Effects of Atorvastatin Combined with Celecoxib on the Proliferation and Apoptosis of Human Colon Cancer SW-480 Cell
|Keywords||Atorvastatin Colon carcinoma Celecoxib bcl-2/bax MMP-9|
Objective: To investigate the effects of HMG-CoA reductases selective inhibitor Atorvastatin with cycloxygenase-2(COX-2) selective inhibitor Celecoxib on cell proliferation and apoptosis of human colon cancer cell line SW-480.To explore its possible mechanisms of anticancer effects.To provides the basis for the drug therapy of colon cancer.Methods: In vitro human colon cancer cell line SW-480 were treated with Atorvastatin and Celecoxib 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 bcl-2,bax,and MMP-9 were determined by reverse transcriplase polymerase chain reaction(RT-PCR). Western Blot was taken to detect bcl-2,bax,and MMP-9 protein expression.Results: MTT assay indicated that the inhibitory effect of Atorvastatin and Celecoxib singly and both on the proliferation of SW-480 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 also great statistical signification between medicated group each other(p<0.05).the inhibitory effct of Atorvastatin combined with Celecoxib was a joint synergy(Q>1.15). Flow cytometry showed that the SW-480 cell cycle was induced by Atorvastatin 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 SW-480 cells apoptosis,and combined use resulted in synergic effect. the expression of bcl-2 and MMP-9 were decreased significantly in the Atorvastatin group and the Atorvastatin combined with Celecoxib group at 48 hours and the bax was increased (p<0.05).Conclusion: Atorvastatin could inhibit the growth of SW-480 cell in dose-and-time dependent maner. It could also induce SW-480 cell apoptosis and arrest cell cycle at the phase of G0/G1. May be the mechanisms of Atorvastatin was through downregulating bcl-2 and MMP-9 and elevating bax expressions .The combinating therapy of Atorvastatin with Celecoxib showed more marked inhibition on the growth of colon carcinoma.