Inhibition of the NF-κB pathway by nafamostat mesilate suppresses colorectal cancer growth and metastasis
Authors: Huai-Qiang Ju
Tie-Bang Kang
Zhi-Zhong Pan
Le-Zong Chen
Hui Sheng
Rui-Hua Xu
Feng Wang
Yun-Xin Lu
Qi-Nian Wu
Hai-Yu Mo
Jing-Ping Yun
Zhao-Lei Zeng
Gong Chen
Dan Xie
Journal: Cancer Letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: Chemoresistance; Colorectal cancer; Nafamostat mesilate; Nuclear factor kappa B; Oxaliplatin.
Affiliations: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China., State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China., State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China., State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China., State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address: .

Abstract:  Nafamostat mesilate is an anti-inflammatory drug that is usually used to treat pancreatitis. Recent studies show that it can suppress pancreatic cancer via inhibition of the nuclear factor κB (NF-κB) pathway. However, whether it has anti-tumor activity in some other cancer, including colorectal cancer (CRC), has not been investigated and remained unclear. Here, our study showed that nafamostat mesilate abrogated the constitutive NF-κB activation in CRC cells, which is mediated through inhibition of phosphorylation of IκBα and nuclear translocation of p65. Also, we found that nafamostat mesilate inhibited phosphorylation of Erk in CRC cells. Consistently, our study demonstrated that nafamostat mesilate inhibited the CRC cell proliferation, invasion and migration and induced mitochondria-dependent apoptosis. Furthermore, nafamostat mesilate could reverse oxaliplatin induced NF-κB and Erk activation in CRC cells, and enhance the sensitivity of CRC cells to oxaliplatin. Nafamostat mesilate combined with oxaliplatin repressed subcutaneous tumor growth and hepatic metastasis in vivo. Overall, our data suggest that nafamostat mesilate, a relatively non-toxic drug that targets NF-κB and Erk, may, in combination with oxaliplatin, represent a novel therapeutic strategy for CRC treatment. 

Retracted: No

PubPeer comments:
 Corrigendum: The authors regret that incorrect images appear in Figure 3B and 4D during data arranging processes. In the published Figure 3B, the flow diagram for HCT116 cells at 24 hour after nafamostat mesilate treatment was incorrectly displayed. In the published Figure 4D, the immunoblotting bands of total-ERK and GAPDH in HCT116 and SW1116 cells were from a different experimental group. This correction does not change the conclusions of this manuscript. Now the corrected Figure 3B and 4D are as below. The authors apologize for the inconvenience. ![file] Original Figures: ![file] ![file] ,