RETRACTED: Effects of Oxymatrine on the Proliferation and Apoptosis of Human Hepatoma Carcinoma Cells
Authors: Yan Liu
Wei Dai
Liqiang Qian
Gang Wang
Tingting Bi
Genhai Shen
Quangen Gao
Journal: Technology in Cancer Research & Treatment (2016)
Discipline: CLINICAL MEDICINE
Keywords: Bax/Bcl-2; apoptosis; caspase; human hepatoma cells; oxymatrine.
Affiliations: Department of General Surgery, Wujiang No. 1 People's Hospital, Suzhou, China., Department of Geriatric Ward, Wujiang No. 1 People's Hospital, Suzhou, China., Department of General Surgery, Wujiang No. 1 People's Hospital, Suzhou, China .

Abstract:  Oxymatrine, one of the main active components of extracts from the dry roots of Sophora flavescens, has been reported to possess anticancer activities in vitro and in vivo However, the precise mechanism involved remains largely unknown. The present study is conducted to investigate the anticancer activity and the underlying mechanisms of oxymatrine in human hepatoma cells (Hep-G2 and SMMC-7721) in vitro and in vivo Hep-G2 and SMMC-7721 cells were treated by oxymatrine and subjected to methyl thiazolyl tetrazolium analysis, Hoechst 33342 staining, annexin V/propidium iodide double staining, reverse transcription polymerase chain reaction, and Western blot analysis. In addition, SMMC-7721 xenograft tumors were established in male nude BALB/c mice, and oxymatrine was intravenously administered to evaluate the anticancer capacity in vivo Our results showed that oxymatrine inhibited the proliferation and induced apoptosis of Hep-G2 and SMMC-7721 cells in a dose-dependent manner in vitro Furthermore, the RNA and protein expression of Bax and caspase 3 levels were significantly upregulated, whereas the expression of Bcl-2 was downregulated. These protein interactions may play a pivotal role in the regulation of proliferation and apoptosis. More importantly, our in vivo studies showed that administration of oxymatrine decreased tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated an increase of Bax and caspase 3 and a decrease of Bcl-2 in tumor tissues following oxymatrine treatment which are consistent with the in vitro results. Taken together, our findings indicated that oxymatrine can inhibit cell proliferation and induce apoptosis of human hepatoma Hep-G2 and SMMC-7721 cells and might offer a therapeutic potential advantage for human hepatoma chemoprevention or chemotherapy. 

Retracted: Yes

PubPeer comments:
 Retracted [24 May 2015] . Suggested by a colleague. -------------------------------------------- The following article has been retracted as a result of our determining the likelihood of manipulation of the peer-review process: u201cEffects of Oxymatrine on the Proliferation and Apoptosis of Human Hepatoma Carcinoma Cells,u201d by Yan Liu, MD, Tingting Bi, MD, Wei Dai, PhD, Gang Wang, PhD, Liqiang Qian, MD, Quangen Gao, MD, and Genhai Shen, MD, Technology in Cancer Research Treatment, DOI: 10.1177 1533034615587616 After investigating the peer-review process for the article, SAGE determined that the peer-review process was likely compromised. Our review identified an unusual verbatim repetition of review comments provided from different peer-reviewer accounts provided by submitting author, Quangen Gao, MD, as recommended reviewers. SAGE apologizes to readers and regrets that the academic record has been compromised as a result of this manipulation of the peer-review process. , 
 *[right]* Figure 7.  Oxymatrine upregulation of Bax and caspase 3, and downregulation of Bcl-2 and Ki67 in SMMC-7721 xenografts. A, Hematoxylin and eosin (H E) staining analyses of the pathological features of the tumors from the 4 groups (original magnification, 400u0004). B-E, The expression of caspase 3, Bax, Bcl-2, and Ki67 in xenograft tumors was analyzed by immunohistochemistry . *[left]*  Fig. 8 from [Liu et al (2015)]  Lupeol downregulates p-AKT, p-ERK, and PCNA in PCNA-1 xenografts. a H E staining analyses of the pathological features of the tumors from the four groups (original magnification, u00d7400). bu2013d The expression of p-AKT, p-ERK, and PCNA in xenograft tumors was analyzed by immunohistochemistry (original magnification, u00d7400). Overlaps marked. Lupeol or Oxymatrin? ![] , 
 *[right]* Figure 7 again.  Oxymatrine upregulation of Bax and caspase 3, and downregulation of Bcl-2 and Ki67 in SMMC-7721 xenografts. A, Hematoxylin and eosin (H E) staining analyses of the pathological features of the tumors from the 4 groups (original magnification, 400u0004). B-E, The expression of caspase 3, Bax, Bcl-2, and Ki67 in xenograft tumors was analyzed by immunohistochemistry . *[left]* Fig 6d from [Liu et al (2016)] .  Combination treatment with OXA [oxaliplatin] and OMT [Oxymatrine] inhibited tumorigenicity in vivo. ... d H E staining analysis of the pathological features of the tumors from the four groups.  ![] Ki67 panels overlap (after 90-deg rotations), despite different labels. , 
 *[below]* Fig 3A.  Oxymatrine treatment induced apoptosis in human hepatoma cells. A, The nuclei were stained by Hoechst 33342 and visualized under fluorescence microscope (original magnification 200u0004) . *[above]* Fig. 3a from [Liu et al (2015)] .  Hoechst staining of PCNA-1 cells treated with 15, 30, and 60 u03bcM lupeol for 36 h. a The nuclei were stained by Hoechst 33342 and visualized under fluorescence microscope (original magnification u00d7200). Two panels appear to be the same. ![file] , 
 Fig 6. It is good that the faces of the mice have been hidden to protect their privacy and right to confidentiality. ![file] , 
 *[right]* Figure 4.  Oxymatrine treatment altered the expression of apoptosis-related molecules in human hepatoma cells. A, Expression of Bax, Bcl-2, and caspase 3 was analyzed by Western blot assay. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as the sample loading control. *[left]* Fig 5 from [Liu et al (2016)] .  Lupeol treatment altered the expression of related molecules in human osteosarcoma cells. A and D, Expression of PI3K, p-PI3K, AKT, p-AKT, mTOR, p-mTOR, p70S6K, p-p70S6K, cyclin D1, p21, and p27 was analyzed by Western blot assay. Glyceraldehydes 3- phosphate dehydrogenase (GAPDH) was used as the sample loading control. Unexpected similarity of the control bands. ![file] , 
 Thank you for pointing out the errors and we apologize the mistakes. We have checked the figure images and indeed found that we misused the images when grouping the figures. Because the experiments and immunohistochemistry related to these articles were basically carried out at the same time, there was a possibility of partial overlap in the preservation of images and the selection of representative images. In addition, a new computer was replaced during data processing, which caused confusion in the storage and processing of some data uff08As fig3 and fig7uff09. Fig 6. Thank you for your comments, we will hidden the faces of the mice to protect their privacy and right to confidentiality. Fig 4. During figure preparationuff0cWe may have used Fig5 as a a template for Fig 4 and forget replacing the GAPDH.We will further verify and correct any errors in time. We will carefully revise the problems in the figures and contact the editor as soon as possible to replace these images. Here, we sincerely apologize for our carelessness. Thank you for your help again. Best Wishes. , 
 *[left]* Figure 7 again.  Oxymatrine upregulation of Bax and caspase 3, and downregulation of Bcl-2 and Ki67 in SMMC-7721 xenografts. A, Hematoxylin and eosin (H E) staining analyses of the pathological features of the tumors from the 4 groups (original magnification, 400u0004). B-E, The expression of **caspase 3, Bax, Bcl-2**, and Ki67 in xenograft tumors was analyzed by immunohistochemistry . *[middle]* rows B and C, rotated through 90 deg, with some panels rotated through 270 deg. *[right]* Figure 7 from [Liu et al (2018)] .  Combination of OMT and CDDP arrests tumor growth.... (d) The expression levels of Ki67, **p-AKT, and p-ERK** in xenograft tumors were determined by immunohistochemical analysis . 8 pairs of overlapping panels, despite different conditions and IHC targets. ![] , 
 Thank you very much for your comments again. We will investigate and look at the original image files to verify if the confusion occurred during these image processing. If so, we will promptly contact the magazine and deal with it. Best wishes , 
 Top to bottom: Fig 3a from [Liu et al (2016a)] .  Combination treatment with OMT and 5-Fu-induced cell apoptosis in HCC cells. a The nuclei were stained by Hoechst 33342 and visualized under fluorescence microscope . At right, panels rotated through 90 and 270 deg. Fig. 3a from [Liu et al (2015)] .  Hoechst staining of PCNA-1 cells treated with 15, 30, and 60 u03bcM lupeol for 36 h. a The nuclei were stained by Hoechst 33342 and visualized under fluorescence microscope . Fig 3a from [Liu et al (2016b)] .  Oxymatrine treatment induced apoptosis in human hepatoma cells. A, The nuclei were stained by Hoechst 33342 and visualized under fluorescence microscope . Fig 3 from [Liu et al (2016c)] .  Apoptotic nuclear morphology changes induced by lupeol (15, 30, and 60 lM) treatment for 36 h, were observed by Hoechst 33342 staining in GBC-SD cell lines . Surprisingly many overlaps, given the differences in cell-lines and conditions. ![file] ,