Celecoxib Induces Apoptosis And Cell-cycle Arrest In Gallbladder Carcinoma Cell Lines Via ERK/JNK/P38 Pathways

Objective:Gallbladder cancer is a kind of common malignant tumor of the biliary tract system,gallbladder cancer is a highly invasive and a very poor prognosis of tumor.Celecoxib is a selective cyclooxygenase-2 inhibitor,in many cancer cell lines showed antitumor effects.However,few studies have reported the antineoplastic effects of Celecoxib on gallbladder cancer cells.In this study,we explored the effects of Celecoxib act on gallbladder cancer and the related mechanism.Methods:Through using MTT and colony formation assays to evaluate the antitumor activity of Celecoxib against EHGB-1 and SGC-996 cells.Using flow cytometry to detect cell apoptosis and cell cycle changes.Western blotting was used to assess the expressions of MAPK/ERK/JNK/P38 signal pathway network-related protein.Finally,by establishing a xenograft SGC-996 model in nude mice to detect the influence of Celecoxib on gallbladder cancer in vivo.Results:The results showed that on MTT and colony formation assay Celecoxib can inhibit gallbladder carcinoma cells of propagation in a dose-dependent and time-dependent manner.A flow cytometry assay revealed in EHGB-1 and SGC-996 cells appeared apoptosis and G0/G1 phase arrest.Celecoxib could down-regulate phosphor-ERK,up-regulate phosphor-JNK and phosphor-p38 expression with dose-dependent manner.In vivo experiment showed Celecoxib can markedly inhibited the growth of xenograft tumor in nude mice and in a dose-dependent manner.Conclusion:These results suggest that Celecoxib play anti-tumor effects by inhibiting cell proliferation,including apoptosis and cell cycle arrest in vitro and in vivo,which may be partly mediated through ERK/JNK/P38 pathways.This findings suggests that Celecoxib may be a novel medicine in the treatment of gallbladder cancer.