Abstract:
A method for treating a cancer includes administering to a subject in need thereof a pharmaceutical composition containing a therapeutically effective amount of Cinacalcet HCl or a pharmaceutical acceptable salt thereof. The cancer is selected from the group consisting of a pleural-related cancer, an abdominal-related cancer, an endocrine-related cancer, a gastrointestinal tract-related cancer, osteosarcoma, skin cancer, and blood cancer.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This is a National Phase Application filed under 35 U.S.C. 371 as a national stage of PCT/CN2015/092776 filed Oct. 23, 2015, an application claiming the benefit under 35 USC 119(e) to the following U.S. Provisional Applications No. 62/068,298 filed Oct. 24, 2014, the content of each of which is hereby incorporated by reference in its entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention related to a new indication of Cinacalcet hydrochloride (Cinacalcet HCl) pharmaceutical composition, especially related to inhibition effect of Cinacalcet hydrochloride (Cinacalcet HCl) pharmaceutical composition on a variety of cancer cells. 
       BACKGROUND OF THE INVENTION 
       [0003]    Cancer is the most popular disease cause of death in the world. The cancer patients are gradually increase yearly, therefore the treatment method of the cancer has become an important issue. The medical treatments of cancer can be classified as surgical treatment, radiation therapy, chemotherapy and target therapy. 
         [0004]    Generally, the cancer drug, whether chemotherapy drug or target therapy drug, is to inhibit cancer cells duplication and split to prevent the tumor growth and metastasis. 
         [0005]    More attention of therapies is being focused on drugs or other substances that block the growth and spread of cancer by interfering with specific molecules (“molecular targets”) that are involved in the growth, progression, and spread of cancer. Averagely, only about five of 10,000 new drugs can successfully enter the phase I of clinical trials. 
         [0006]    Otherwise, the manufacturing of the drug is still a big problem. When the drug starting the clinical trials, there are lots of problems need to overcome, such as drug safety, patient selection, trial dose and other issues. Even the drug has approved by the FDA and sales on the market, there still possibly face the situation of the poor drug response in patients. Furthermore, if the cancer patients happen the drug resistance, that would reduce the effectiveness of the drugs and result in the medical treatment failure. Therefore, the new drug development is very difficult. 
         [0007]    Cinacalcet hydrochloride (Cinacalcet HCl) or calcimimetic is a naphthalene derivative and calcimimetic agent that increases the sensitivity of parathyroid gland calcium-sensing receptors to serum calcium. (Cinacalcet HCl) is the orally bioavailable hydrochloride salt of the calcimimetic cinacalcet. Cinacalcet increases the sensitivity of calcium-sensing receptors on chief cells in the parathyroid gland to extracellular calcium, thereby reducing parathyroid hormone (PTH) secretion. In other word, these actions could reduce parathyroid hormone secretion and decreases serum calcium in the treatment of parathyroid disease. Further, a reduction in PTH levels inhibits osteoclast activity, which may result in a decrease in cortical bone turnover and bone fibrosis, and normalization of serum calcium and phosphorus levels. In another way, Cinacalcet HCl therapy was used for secondary hyperparathyroidism in hemodialysis patients. As a result, Cinacalcet HCl is approved by FDA and accumulated a huge data of drug use and drug mechanism research. 
         [0008]    Due to the differences of the clinical use, there is no research present that the Cinacalcet HCl has any potential to inhibit cancer cell. 
       SUMMARY OF THE INVENTION 
       [0009]    In order to solve the above problems, the present invention provides the development of new cancer clinical indications of Cinacalcet HCl. 
         [0010]    Accordingly, the present invention provides a new indication of Cinacalcet HCl. The experimental results showed that the Cinacalcet HCl had no toxicity or had little toxicity to normal cells in the present invention. However, the selective effect of Cinacalcet HCl between normal cells and cancer cells need to be identified. 
         [0011]    The present invention provides a pharmaceutical composition of Cinacalcet HCl for treating cancer. The pharmaceutical composition is composed of effective dose of Cinacalcet HCl and a pharmaceutical acceptable salt. 
         [0012]    In one embodiment of the present invention, the cancer is selected from pleural-related cancer, abdominal-related cancer, endocrine-related cancer, gastrointestinal tract-related cancer. 
         [0013]    In one embodiment of the present invention, the cancer is selected from osteosarcoma, skin cancer and blood cancer. 
         [0014]    In one embodiment of the present invention, the pleural-related cancer is lung cancer. 
         [0015]    In one embodiment of the present invention, the abdominal-related cancer is selected from bladder cancer, and cervical cancer. 
         [0016]    In one embodiment of the present invention, the endocrine-related cancer is selected from prostate cancer, breast cancer, and ovarian cancer. 
         [0017]    In one embodiment of the present invention, the gastrointestinal tract-related cancer is selected from gastric cancer, hepatic cancer, colorectal cancer, pancreatic cancer, and tongue cancer. 
         [0018]    In one embodiment of the present invention, the effective dose of Cinacalcet HCl is from 10 mg/kg/day to 500 mg/kg/day. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0019]      FIG 1  shows the inhibitory effect of Cinacalcet HCl on the different cancer cells. 
           [0020]      FIG. 2  shows the results of the inhibitory effect of tumor volume by Cinacalcet HCl. 
           [0021]      FIG. 3  shows the inhibitory effect of tumor growth via administered high-dose and low-dose of Cinacalcet HCl. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0022]    Cell Culture 
         [0023]    Subculture the different types of cancer cells. The cancer cells includes lung cancer, gastric cancer, hepatic cancer, colon cancer, skin cancer, cervical cancer, prostate cancer, bladder cancer, breast cancer, leukemia, pancreatic cancer, ovarian cancer, tongue cancer, osteosarcoma, and renal cancer. The normal cells used in the control group included kidney cell (HEK293) and human bronchial epithelial cell line BEAS-2B (as shown in Table 1). 
         [0024]    Cancer cell lines were cultured in different culture medium according to different characteristics (as shown in Table 1). The cell numbers were counted and reseed as 2×10 6  in culture plate/flask. Then, the culture medium were added to a volume of 10 ml, and the cells were cultured for 2-3 days. Then, the cells were suspended for loading into 96-well plates. The number of cells was 3000 and the volume of the culture medium was 100 μl each well. 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Cancer cell lines and culture medium 
               
             
          
           
               
                 No 
                 Cancer type 
                 Cancer cell type 
                 Culture medium 
               
               
                   
               
             
          
           
               
                 1 
                 lung cancer 
                 H1650 (lung adenocarcinoma) 
                 RPMI-1640 
               
               
                   
                   
                 A549 (lung adenocarcinoma) 
                 DMEM 
               
               
                 2 
                 gastric cancer 
                 AGS (Gastric Adenocarcinoma) 
                 RPMI-1640 
               
               
                   
                   
                 MKN-45 (Gastric Adenocarcinoma) 
                 RPMI-1640 
               
               
                 3 
                 hepatic cancer 
                 HepG2 (hepatocellular carcinoma) 
                 DMEM 
               
               
                   
                   
                 Hep3B (hepatocellular carcinoma) 
                 DMEM 
               
               
                 4 
                 colon cancer 
                 HCT116(p53+) (colorectal carcinoma) 
                 DMEM 
               
               
                   
                   
                 LoVo(Colorectal Adenocarcinoma) 
                 DMEM 
               
               
                 5 
                 skin cancer 
                 A375 (amelanotic melanoma) 
                 DMEM 
               
               
                   
                   
                 BCC (basal cell carcinoma) 
                 DMEM 
               
               
                 6 
                 cervical cancer 
                 HeLa (Cervix Adenocarcinoma) 
                 DMEM 
               
               
                   
                   
                 C-33A (Cervical carcinoma) BCRC60554 
                 MEM 
               
               
                 7 
                 prostate cancer 
                 PC3 (p53−)(Prostate adenocarcinoma) 
                 DMEM 
               
               
                   
                   
                 LNCaP clone FGC (LNCap.FGC) 
                 RPMI-1640 
               
               
                 8 
                 bladder cancer 
                 8301 (urinary bladder carcinoma) 
                 RPMI-1640 
               
               
                   
                   
                 T24 
                 RPMI-1640 
               
               
                 9 
                 breast cancer 
                 MCF7 (Mammary Gland, Adenocarcinoma) 
                 DMEM 
               
               
                   
                   
                 MDA-MB-231 (Mammary Gland, Adenocarcinoma) 
                 DMEM 
               
               
                 10 
                 pancreatic cancer 
                 BxPC-3 
                 RPMI-1640 
               
               
                   
                   
                 AsPC-1 
                 RPMI-1640 
               
               
                 11 
                 ovarian cancer 
                 NIH: OVCAR-3 
                 RPMI-1640 
               
               
                   
                   
                 TOV-21G 
                 RPMI-1640 
               
               
                 12 
                 tongue cancer 
                 SAS (Tongue squamous cell carcinoma) 
                 DMEM 
               
               
                 13 
                 osteosarcoma 
                 U-2OS 
                 DMEM 
               
               
                 14 
                 renal cancer 
                 786-O (Renal adenocarcinoma) BCRC 60243 
                 RPMI-1640 
               
               
                 15 
                 normal cell kidney 
                 HEK293 (Kidney) 
                 DMEM 
               
               
                   
                 pulmonary epithelial 
                 BEAS-2B (Lung Epithelial) 
                 RPMI-1640 
               
               
                   
                 cell line 
               
               
                   
               
             
          
         
       
     
         [0025]    Cell Viability Analysis 
         [0026]    Removing the original culture medium from 96-well plate. Then add 100 μl of commercially drug at a concentration of 10 μM per well. After 72 hours, add the diluted WST-1 reagent to the well with 100 μl/well, and the diluted WST-1 reagent was acquired from the dilution of 9:1 medium and WST-1 stock reagent. Finally, the total volume of each well was 200 μl/well. Culture the 96-well plate at 37° C. for 30 to 90 minutes. Detecting and calculate the survival rate of each cancer cells with an ELISA reader at OD450 nm. The lower viability of cancer cells represents better inhibition effect via the Cinacalcet HCl drug. Otherwise, the higher viability of cancer cells represents worse inhibition effect via the Cinacalcet HCl drug. 
         [0027]    The Effect of Cinacalcet HCl on Different Cancer Cell Lines 
         [0028]    The Inhibition Effect of Cinacalcet HCl on Pleural-Related Cancer Cells 
         [0029]    This inhibition test of Cinacalcet HCl on pleural-related cancer cells were using two lung cancer cell lines A549 and H1650. The inhibitory tests of Cinacalcet HCl were performed 4 times for each cell lines and then the average value of the inhibitory tests was calculated. The results were shown in Table 2. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 2 
               
               
                   
               
               
                 The inhibition effect of Cinacalcet HCl on pleural-related cancer cells 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 0524-10 
                   
                   
                   
                   
               
               
                   
                 min 
                 0526-10 min 
                 0529-10 min 
                 0531-10 min 
                 Average 
               
               
                   
               
               
                 A549 
                 87.7 
                 102.7 
                 75.5 
                 92.6 
                 89.6 
               
               
                   
               
               
                   
                 1-10 min 
                 2-20 min 
                 3-20 min 
                 4-20 min 
                 Average 
               
               
                   
               
               
                 H1650 
                 86.8 
                 67.5 
                 76.8 
                 75.2 
                 76.5 
               
               
                   
               
             
          
         
       
     
         [0030]    The Inhibition Effect of Cinacalcet HCl on Abdominal-Related Cancer Cell Lines 
         [0031]    This inhibition test of Cinacalcet HCl on abdominal-related cancer cells were using bladder cancer cell line TSGH and T24 (Table 3), cervical cancer cell lines HeLa and C-33A (Table 4), renal cancer cell line 786-O (Table 5). The inhibitory tests of Cinacalcet HCl were performed 4 times for each cell lines and then the average value of the inhibitory tests was calculated. The results were shown in Table 3, Table 4, and Table 5. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 3 
               
               
                   
               
               
                 The inhibition effect of Cinacalcet HCl on bladder cancer cell lines 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 0510-10 
                   
                   
                   
                   
               
               
                   
                 min 
                 0512-10 min 
                 0515-10 min 
                 0517-10 min 
                 average 
               
               
                   
               
               
                 TSGH 
                 57.3 
                 73.2 
                 74.7 
                 33.9 
                 59.8 
               
               
                   
               
               
                   
                 T24-1-30 
                 T24-2-20 
                 T24-3-20 
                 T24-4-20 
                   
               
               
                   
                 min 
                 min 
                 min 
                 min 
                 average 
               
               
                   
               
               
                 T24 
                 71.1 
                 132.6 
                 177.1 
                 103.3 
                 121.0 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 The inhibition effect of Cinacalcet HCl on cervical cancer cell lines 
               
             
          
           
               
                   
                 0524-10  
                 0526-10  
                 0529-10  
                 0531-10  
                   
               
               
                   
                 min 
                 min 
                 min 
                 min 
                 average 
               
               
                   
               
               
                 HeLa 
                 109.6 
                 118.6 
                 104.1 
                 113.0 
                 111.3 
               
               
                 C-33A 
                 114.5 
                 118.8 
                 108.1 
                 100.0 
                 110.3 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 The inhibition effect of Cinacalcet HCl on renal cancer cell lines 
               
             
          
           
               
                   
                 0524-10 min 
                 0526-10 min 
                 0529-10 min 
                 0531-10 min 
                 average 
               
               
                   
               
               
                 786-O 
                 81.3 
                 71.6 
                 80.2 
                 87.1 
                 80.0 
               
               
                   
               
             
          
         
       
     
         [0032]    The Inhibition Effect of Cinacalcet HCl on Endocrine-Related Cancer Cell Lines 
         [0033]    This inhibition test of Cinacalcet HCl on endocrine-related cancer cells were using prostate cancer cell lines PC-3 and LNCap (Table 6), breast cancer cell lines MCF7 and MDA-MB-231 (Table 7), and ovarian cancer cell lines NIH-OVCAR-3 and TOV-21G (Table 8). The inhibitory tests of Cinacalcet HCl were performed 4 times for each cell lines and then the average value of the inhibitory tests was calculated. The results were shown in Table 6, Table 7, and Table 8. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
             
           
               
                 TABLE 6 
               
             
             
               
                   
               
               
                 The inhibition effect of Cinacalcet HCl on prostate cancer cell lines 
               
             
          
           
               
                   
                 PC-3- 
                 PC-3- 
                 PC-3- 
                 PC-3- 
                   
               
               
                   
                 0524-10 
                 0526-10 
                 0529-10 
                 0531-10 
                   
               
               
                   
                 min 
                 min 
                 min 
                 min 
                 average 
               
               
                   
               
               
                 PC-3 
                 102.7 
                 132.2 
                 120.3 
                 134.6 
                 122.5 
               
             
          
           
               
                   
                 Average 
               
               
                 LNCap 
                 52.6 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 7 
               
             
             
               
                   
               
               
                 The inhibition effect of Cinacalcet  
               
               
                 HCl on breast cancer cell lines 
               
             
          
           
               
                   
                 0612-10  
                 0614-10  
                 0616-10  
                 0619-10  
                   
               
               
                   
                 min 
                 min 
                 min 
                 min 
                 average 
               
               
                   
               
               
                 MCF7 
                 87.7  
                 75.6  
                 82.2  
                 77.2  
                 80.7  
               
               
                 MDA- 
                 92.35 
                 84.94 
                 60.81 
                 92.75 
                 82.71 
               
               
                 MB-231 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 8 
               
             
             
               
                   
               
               
                 The inhibition effect of Cinacalcet HCl on ovarian cancer cell lines 
               
             
          
           
               
                   
                 7-3-30 min 
                 7-4-30 min 
                 7-7-30 min 
                 -4-30 min 
                 average 
               
               
                   
               
               
                 NIH-OVCAR-3 
                  90.7 
                 111.1 
                 100.2 
                 111.0 
                 103.3 
               
               
                 TOV-21G 
                 128.7 
                 109.4 
                 104.1 
                 108.2 
                 112.6 
               
               
                   
               
             
          
         
       
     
         [0034]    The Inhibition Effect of Cinacalcet HCl on Gastrointestinal Tract-Related Cancer Cell Lines 
         [0035]    This inhibition test of Cinacalcet HCl on gastrointestinal tract-related cancer cells were using gastric cancer cell lines AGS and MKN-45 (Table 9), hepatic cancer cell lines HepG2 and Hep3B (Table 10), colorectal cancer cell lines HCT116-wt and LoVo (Table 11), pancreatic cancer cell line AsPC-1 and BxPC-3(Table 12), tongue cancer cell line SAS (Table 13). The inhibitory tests of Cinacalcet HCl were performed 4 times for each cell lines and then the average value of the inhibitory tests was calculated. The results were shown in Table 9, Table 10, Table 11, Table 12 and Table 13. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 9 
               
             
             
               
                   
               
               
                 The inhibition effect of Cinacalcet HCl on gastric cancer cell lines 
               
             
          
           
               
                   
                 0510-10  
                 0512-10  
                 0515-10  
                 0517-10  
                   
               
               
                   
                 min 
                 min 
                 min 
                 min 
                 average 
               
               
                   
               
               
                 AGS 
                 26.6 
                  20.0 
                  52.3 
                 14.50856943 
                 28.3 
               
               
                 MKN-45 
                 82.1 
                 101.5 
                 103.6 
                 69.1     
                 89.1 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 10 
               
               
                   
               
               
                 The inhibition effect of Cinacalcet HCl on hepatic cancer cell lines 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 0524-20  
                 0526-20  
                 0529-20  
                 0531-20  
                   
               
               
                   
                 min 
                 min 
                 min 
                 min 
                 average 
               
               
                   
               
               
                 HepG2 
                 105.7 
                 132.6 
                 116.5 
                  89.5 
                 111.1 
               
               
                   
               
               
                   
                 0612-20  
                 0614-20  
                 0616-20  
                 0619-20  
                   
               
               
                   
                 min 
                 min 
                 min 
                 min 
                 average 
               
               
                   
               
               
                 Hep3B 
                 143.2 
                 125.1 
                 151.5 
                 116.8 
                 134.1 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 11 
               
               
                   
               
               
                 The inhibition effect of Cinacalcet HCl on colorectal cancer cell 
               
               
                 lines 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 0602-30  
                 0605-10  
                 0607-10  
                 0609-10  
                   
               
               
                   
                 min 
                 min 
                 min 
                 min 
                 average 
               
               
                   
               
               
                 HCT116-wt 
                 89.0 
                 107.3 
                 132.5 
                 112.6 
                 110.3 
               
               
                   
               
               
                   
                 0616-10  
                 0619-10  
                 0621-10  
                 0623-10  
                   
               
               
                   
                 min 
                 min 
                 min 
                 min 
                 average 
               
               
                   
               
               
                 LoVo 
                 73.9 
                 125.0 
                  90.4 
                  84.2 
                  93.4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 12 
               
               
                   
               
               
                 The inhibition effect of Cinacalcet HCl on pancreatic cancer cell 
               
               
                 lines 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 1-7-3-30 min 
                 1-7-4-30 min 
                 1-7-7-30 min 
                 1-4-30 min 
                 Average 
               
               
                   
               
               
                 AsPC-1 
                 61.6 
                 81.7 
                  60.4 
                 71.9 
                 68.9 
               
               
                   
               
               
                   
                 3-7-3-30 min 
                 3-7-4-30 min 
                 3-7-7-30 min 
                 3-4-30 min 
                 Average 
               
               
                   
               
               
                 BxPC-3 
                 64.6 
                 78.8 
                 100.1 
                 76.2 
                 79.9 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 13 
               
             
             
               
                   
               
               
                 The inhibition effect of Cinacalcet HCl on tongue cancer cell lines 
               
             
          
           
               
                   
                 6-26-10 min 
                 6-28-10 min 
                 6-30-10 min 
                 7-3-10 min 
                 average 
               
               
                   
               
               
                 SAS 
                 45.7 
                 88.9 
                 96.2 
                 98.9 
                 82.4 
               
               
                   
               
             
          
         
       
     
         [0036]    The Inhibition Effect of Cinacalcet HCl on Other Cancer Cell Lines 
         [0037]    This inhibition test of Cinacalcet HCl on other cancer cells were using osteosarcoma cell line U2OS (Table 14), skin cancer cell lines A375 and BCC (Table 15). The inhibitory tests of Cinacalcet HCl were performed 4 times for each cell lines and then the average value of the inhibitory tests was calculated. The results were shown in Table 14 and Table 15. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 14 
               
             
             
               
                   
               
               
                 The inhibition effect of Cinacalcet HCl on osteosarcoma cancer cell 
               
               
                 line 
               
             
          
           
               
                   
                 6-26-10 min 
                 6-28-10 min 
                 6-30-10 min 
                 7-3-10 min 
                 average 
               
               
                   
               
               
                 U2OS 
                 82.6 
                 86.7 
                 64.9 
                 75.3 
                 77.4 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 15 
               
               
                   
               
               
                 The inhibition effect of Cinacalcet HCl on skin cancer cell lines 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 0602-30 min 
                 0605-10 min 
                 0607-10 min 
                 0609-10 min 
                 average 
               
               
                   
               
               
                 A375 
                 117.1 
                  95.6 
                  94.4 
                 108.5 
                 103.9 
               
               
                   
               
             
          
           
               
                   
                 0602-30 min 
                 0605-10 min 
                 0607-10 min 
                 average 
               
               
                   
               
               
                 BCC 
                 114.2 
                 105.5 
                 112.6 
                 110.8 
               
               
                   
               
             
          
         
       
     
         [0038]    The Experiment Design on Control Group 
         [0039]    The Inhibition Effect of Cinacalcet HCl on Normal Cells 
         [0040]    This inhibition test of Cinacalcet HCl on normal cells were using normal kidney cell line HEK293 (Table 16), normal pulmonary epithelial cell lines canine fibroblast cell line BEAS-2B (Table 17). The inhibitory tests of Cinacalcet HCl were performed 4 times for each cell lines and then the average value of the inhibitory tests was calculated The results were shown in Tables 16 and Tables 17. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 16 
               
             
             
               
                   
               
               
                 The inhibition effect of Cinacalcet HCl  
               
               
                 on normal kidney cell line  
               
             
          
           
               
                   
                   
                 average 
               
               
                   
                   
               
               
                   
                 HEK293 
                 114.1 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 17 
               
             
             
               
                   
               
               
                 The inhibition effect of Cinacalcet HCl on normal pulmonary 
               
               
                 epithelial cell line 
               
             
          
           
               
                   
                 0510-10  
                 0512-10  
                 0515-10  
                 0517-10  
                   
               
               
                   
                 min 
                 min 
                 min 
                 min 
                 average 
               
               
                   
               
               
                 BEAS-2B 
                 70.5 
                 72.9 
                 72.2 
                 89.0 
                 76.1 
               
               
                   
               
             
          
         
       
     
         [0041]    This inhibition test results of Cinacalcet HCl on all kinds of cells were shown in Table 18. Cinacalcet HCl is having different inhibitory effect on different tumor cell type even in the same cancer. As a result in the experiments of the present invention, Cinacalcet HCl has a significant inhibitory effect and specificity on various cancer cells. ( FIG. 1 ) 
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 18 
               
             
             
               
                   
               
               
                 Summary of the Effect on different cancer  
               
               
                 cell lines by Cinacalcet HCl 
               
             
          
           
               
                   
                 cancer cells 
                 Inhibitory effect 
               
               
                   
                   
               
             
          
           
               
                   
                 lung cancer 
                 83.09384194 
               
               
                   
                 bladder cancer 
                 90.4 
               
               
                   
                 cervical cancer 
                 111.32 
               
               
                   
                 Kidney cancer 
                 87.53 
               
               
                   
                 prostate cancer 
                 81.70 
               
               
                   
                 breast cancer 
                 107.9 
               
               
                   
                 ovarian cancer 
                 58.7 
               
               
                   
                 gastric cancer 
                 122.60 
               
               
                   
                 hepatic cancer 
                 101.85 
               
               
                   
                 colorectal cancer 
                 74.4 
               
               
                   
                 pancreatic cancer 
                 82.44 
               
               
                   
                 tongue cancer 
                 77.37 
               
               
                   
                 osteosarcoma 
                 107.32 
               
               
                   
                 skin cancer 
                 80.0 
               
               
                   
                 kidney cell lines 
                 114.06 
               
               
                   
                 normal pulmonary epithelial  
                 76.13 
               
               
                   
                 cell line 
               
               
                   
                   
               
             
          
         
       
     
         [0042]    Animal Model Test of Gastric Cancer with Dose 100 mg/kg/day and 200 mg/kg/day 
         [0043]    In this invention, the female mice were(BALB/cAnN.Cg-Foxnl™/CrlNarl) and purchased from National Laboratory Animal Center (Taiwan). The weight of the mice were 21±1 g. These mice were subcutaneously injected with gastric cancer cells (AGS) and then put these mice into different cages at random. The drug test experiment was divided into three groups, include “control group”, “low dose group (100 mg/kg/day)”, “high dose group (200 mg/kg/day)”. These mice were then injected test drug intraperitoneally once daily until the tumor size reached 100 mm 3 . The tumor sizes and body weight were measured twice a week. The tumor sizes were measured and calculated by formula: (L×W 2 )/2. L represents the tumor longest length. W represents the tumor shortest diameter. The experiment result is shown in Table 19. 
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 19 
               
             
             
               
                   
               
               
                 The inhibitory effect of tumor volume via administered Cinacalcet 
               
               
                 HCl 
               
             
          
           
               
                 control group 
                 Low dose (100 mg/kg/day) 
                 high dose (200 mg/kg/day) 
               
             
          
           
               
                   
                   
                   
                   
                   
                 tumor 
                   
                   
                   
                   
                 tumor 
                   
                   
                   
                   
                 tumor 
               
               
                   
                   
                 longest 
                   
                 vol- 
                 volume 
                   
                 longest 
                   
                   
                 volume 
                   
                 longest 
                   
                   
                 volume 
               
               
                   
                 weight 
                 length 
                 width 
                 ume 
                 growth 
                 weight 
                 length 
                 width 
                 volume 
                 growth 
                 weight 
                 length 
                 width 
                 volume 
                 growth 
               
               
                   
                 (g) 
                 mm 
                 mm 
                 mm3 
                 mm3 
                 (g) 
                 mm 
                 mm 
                 mm3 
                 mm3 
                 (g) 
                 mm 
                 mm 
                 mm3 
                 mm3 
               
               
                   
                   
               
             
          
           
               
                 First measurement 
               
             
          
           
               
                 A 
                 18.5 
                 7 
                 7 
                 171.5 
                 171.5 
                 20 
                 11 
                 8 
                 352 
                 352 
                 19 
                 7 
                 5 
                 87.5 
                 87.5 
               
               
                 B 
                 22 
                 8 
                 6 
                 144 
                 144 
                 16 
                 13 
                 8 
                 416 
                 416 
                 19.5 
                 6 
                 6 
                 108 
                 108 
               
               
                 C 
                 20.5 
                 9 
                 8 
                 288 
                 288 
                 21 
                 14 
                 12 
                 1008 
                 1008 
                 1.5 
                 6 
                 4 
                 48 
                 48 
               
               
                 aver- 
                 20.4 
                 7.6 
                 7 
                 189.3 
                 189.3 
                   
                   
                   
                 592 
                 592 
                   
                   
                   
                 81.16667 
                 81.16667 
               
               
                 age 
               
             
          
           
               
                 Second measurement 
               
             
          
           
               
                 A 
                 22 
                 7 
                 6 
                 126 
                 −45.5 
                 21 
                 8 
                 5 
                 100 
                 −252 
                 18.5 
                 7 
                 7 
                 171.5 
                 84 
               
               
                 B 
                 20 
                 8 
                 7 
                 196 
                 52 
                 22 
                 16 
                 8 
                 512 
                 96 
                 21 
                 6 
                 7 
                 147 
                 39 
               
               
                 C 
                 20 
                 9 
                 7 
                 220.5 
                 −67.5 
                 19 
                 9 
                 7 
                 220.5 
                 −787.5 
                 19 
                 6 
                 5 
                 75 
                 27 
               
               
                 aver- 
                 20.6 
                 8.4 
                 6.8 
                 198.5 
                 9.2 
                   
                   
                   
                 277.5 
                 −314.5 
                   
                   
                   
                 131.1667 
                 50 
               
               
                 age 
               
             
          
           
               
                 Third measurement 
               
             
          
           
               
                 A 
                 23 
                 9 
                 6 
                 162 
                 36 
                 23.5 
                 19 
                 15 
                 2137.5 
                 2037.5 
                 19 
                 7 
                 5 
                 87.5 
                 −84 
               
               
                 B 
                 20 
                 10 
                 8 
                 320 
                 124 
                 21 
                 7 
                 6 
                 126 
                 −386 
                 22 
                 6 
                 5 
                 75 
                 −72 
               
               
                 C 
                 21 
                 11 
                 7 
                 269.5 
                 49 
                 21 
                 8 
                 6 
                 144 
                 −76.5 
                 18.5 
                 6 
                 5 
                 75 
                 0 
               
               
                 aver- 
                 21.2 
                 10 
                 6.8 
                 235.3 
                 36.8 
                   
                   
                   
                 802.5 
                 525 
                   
                   
                   
                 79.16667 
                 −52 
               
               
                 age 
               
             
          
           
               
                 Fourth measurement 
               
             
          
           
               
                 A 
                 22 
                 12 
                 8 
                 384 
                 114.5 
                 22 
                 10 
                 7 
                 245 
                 −1892.5 
                 23 
                 6 
                 3 
                 27 
                 −60.5 
               
               
                 B 
                 22 
                 11 
                 8 
                 352 
                 172 
                 22 
                 14 
                 7 
                 343 
                 217 
                 23 
                 5 
                 4 
                 40 
                 −35 
               
               
                 C 
                 23 
                 12 
                 9 
                 486 
                 134 
                 23 
                 13 
                 13 
                 1098.5 
                 954.5 
                 20 
                 0 
                 0 
                 0 
                 −75 
               
               
                 aver- 
                 22.4 
                   
                   
                 295.7 
                 62.2 
                   
                   
                   
                 562.1667 
                 −240.3333 
                   
                   
                   
                 22.33333 
                 −56.8333 
               
               
                 age 
               
               
                   
               
             
          
         
       
     
         [0044]    According to the results in  FIG. 2 , both low dose and high dose of Cinacalcet HCl had significant inhibition effect on tumor cells, and the weight of mice did not show a significant decrease during the experiment. These results indicated that both high and low doses of Cinacalcet HCl could keep the tested mice in healthy status during the treatment without death. 
         [0045]    According to the results in  FIG. 3 , both low dose and high dose of Cinacalcet HCl had effectively slow down the tumor volume growth, and can also reduce the tumor volume. Especially, high doses of Cinacalcet HCl had better effect to inhibit tumor growth. 
         [0046]    Although the present invention has been described in terms of specific exemplary embodiments and examples, it will be appreciated that the embodiments disclosed wherein are for illustrative purposes only and various modifications and alterations might be made by those skilled in the art without departing from the spirit and scope of the invention as set forth in the following claims.