Combination chemotherapy of nafamostat mesilate with gemcitabine for pancreatic cancer targeting NF-κB activation

Purpose: Gemcitabine is currently the standard first-line chemotherapeutic agent for pancreatic cancer. However, chemoresistance to gemcitabine because of gemcitabine-induced nuclear factor-κB (NF-κB) activation has been reported. We previously reported that the synthetic serine protease inhibitor nafamostat mesilate inhibited NF-κB activation and induced apoptosis of pancreatic cancer cells. In this study, whether or not nafamostat mesilate could enhance the anticancer effect of gemcitabine was investigated. Materials and Methods: NF-κB activation in pancreatic cancer cells treated with various agents was examined by electrophoretic mobility shift assay (in vitro) and immunohistochemistry by investigating the location of p65 in cancer cells (in vivo). Apoptosis of the cancer cells treated with agents was examined by flow cytometry. Results: Nafamostat mesilate inhibited gemcitabine-induced NF-κB activation, enhanced apoptosis by gemcitabine and suppressed pancreatic tumor growth. Interestingly, the combination treatment improved the body weight loss of mice induced by gemicitabine. Conclusion: This combination chemotherapy could be a potential novel strategy for pancreatic cancer.