Proliferation inhibition induced by Nimesulide through PPARγpathway in human colon cancer cell / 重庆医学

ABSTRACT

Objective To study PPARγ inhibitor(GW9662) ,on colon cancer SW480 cell proliferation and apoptosis intervened by Nimesulide(N) in vitro ,in order to investigate the role of PPARγpathway in colon cancer cell proliferation inhibition and apop‐tosis promotion induced by Nimesulide .Methods Cells were divided into 4 groups ,namelythe control group ,GW9662 group (GW9662 0 .1 ,0 .5 ,1 .0 ,5 .0μmol/L) ,N group ,GW9662+N group .MTT assay and FCM were used to determine proliferation ,ap‐optosis and cell cycle of SW480 cells .And the expression of PPARγ,p21Waf1 ,p27Kip1 ,Bcl‐2 ,Bax ,VEGF proteins were measured by Western‐blot .Results N inhibited SW480 cells proliferation in a time‐dependent manner (P0 .05) . Cell apoptosis rate of group N increased significantly ,compared with control group(P<0 .01) .The apoptosis rates of SW480 cells incubated with Nimesulide and GW9662 dropped significantly compared with Nimesulide alone (P<0 .01) .Above results showed that GW9662 could attenuate the effect of nimesulide on cell apoptosis and cell cycle .The results of Western‐blotCompared with the control group ,the expression of PPARγ,p21Waf1 ,p27Kip1 ,Bax protein were up‐regulated significantly in nimesulide group(P<0 .05 or P<0 .01) ,but Bcl‐2 and VEGF were down‐regulated significantly(P<0 .01) .Compared with the nimesulide group ,the expres‐sion of PPARγ,p21Waf1 , p27Kip1 and Bax protein were down‐regulated obviously in GW9662+N group(P<0 .05 or P<0 .01) .Corre‐spondingly ,Bcl‐2 and VEGF were up‐regulated obviously(P<0 .05) .Conclusion N could effectively inhibit SW480 cell prolifera‐tion and induce its apoptosis .PPARγpathway may play an important role in proliferation inhibition and apoptosis induced by Nime‐sulide in colon cancer cell .