Effects Of Celecoxib Combined With Oxaliplatin On The Proliferation And Apoptosis Of Human Colon Cancer HCT-116 Cell

Objective: To investigate the effects of cycloxygenase-2(COX-2) selective inhibitor Celecoxib with Oxaliplatin(L-OHP) on cell proliferation and apoptosis of human colon cancer cell line HCT-116.also to explore its possible mechanisms of anticancer effects.Methods: In vitro,human colon cancer cell line HCT-116 were treated with Celecoxib and Oxaliplatin singly and both of them.by means of MTT assay,the absorbance value was detected and growth inhibition rate was calculated.Cell cycle and apoptosis was assessed by flow cytometry;The changes of cell morphology were observed by inverted and confocal microcope. the mRNA expressions of survivin and VEGF were determined by reverse transcriplase polymerase chain reaction(RT-PCR). Western Blot was taken to detect survivin and VEGF protein expression.Results: MTT assay indicated that the inhibitory effect of Celecoxib and Oxaliplatin singly and both on the proliferation of HCT-116 cell was found in dose-and-time dependent manner. There was great statistical signification between varies medicated group and control group(P<0.05),and there also were great statistical signification between medicated group each other(P<0.05).the inhibitory effct of Celecoxib combined with Oxaliplatin was a joint synergy(Q>1.15). Flow cytometry showed that the HCT-116 cell cycle was induced by Celecoxib at 48 hours,the ratio of G0/G1 phase was increased and the ratio of S phase was decreased significantly (P<0.05). meanwhile, both of the two drugs induced HCT-116cells apoptosis,and combined use resulted in synergic effect. the expression of Survivin and VEGF were decreased significantly in the Celecoxib group and the Celecoxib combined with Oxaliplatin group at 48 hours(P<0.05). Conclusion: Celecoxib could inhibit the growth of HCT-116 cell in dose-and-time dependent maner. it could also induce HCT-116 cell apoptosis and arrest cell cycle at the phase of G0/G1. May be celecoxib's mechanisms was through downregulating survivin and VEGF expressions .The combinating therapy of Celecoxib with L-OHP showed more marked inhibition on the growth of colon carcinoma.