Abstract
Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor with high incidence and an average age of onset of 50-70 years old. However, at present there is no effective treatment for this disease. The aim of the present study was to investigate the effects of a c-Met inhibitor, PF-2341066 and a cyclooxygenase-2 (COX-2) inhibitor, celecoxib, on c-Met and COX-2 expression, proliferation and apoptosis. The results demonstrated that c-Met and COX-2 are highly expressed in hepatobiliary calculus with cholangiocarcinoma. PF-2341066 was able to downregulate the expression of c-Met and COX-2 in a dose-dependent manner at the mRNA and protein levels in human cholangiocarcinoma QBC939 cells. Furthermore, combined treatment with PF-2341066 with celecoxib downregulated the mRNA expression of both genes, inhibited cell proliferation and promoted cell apoptosis. It was also demonstrated that PF-2341066 and celecoxib treatment was able to restrict the expression of vascular endothelial growth factor (VEGF). The results of the present study suggest that PF-2341066 and celecoxib may inhibit the development of cholangiocarcinoma by downregulating the expression of c-Met and COX-2 to inhibit cell proliferation, promote apoptosis and prevent VEGF-mediated tumor angiogenesis. Co-treatment with PF-2341066 and celecoxib may be a potential therapeutic strategy for hepatobiliary calculus with cholangiocarcinoma.