Studiy on celecoxib inducing gastric cancer cell apoptosis and its mechanism

Objective:To investigate the effect and mechanism of celecoxib,a selective cyclooxygenase-2 inhibitor,on inhibiting the proliferation and inducing apoptosis in gastric cancer cell line MKN-45.Methods:MTT assay was used to study the inhibitive effect of celecoxib on the growth of gastric cancer cell.The effect of celecoxib on cell cycle changes and apoptosis of cells was studied by flow cytometry(FCM).The expression of Bax and Bcl-2 proteins were measured by immunohistochemistry.Ultramicrostructure was observed through transmission electron microscope(TEM).DNA gel electrophoresis was performed for assessing the effect of celecoxib on DNA apoptotic ladder.Results:It was observed that after treatment with celecoxib,the proliferations of MKN-45 cell were inhibited in a dose-and time-dependent manner.After being exposed to various concentrations of celecoxib(25,50,75 and 100μmol/L) for 24h,the inhibitive rates on MKN-45 were(16.39±1.43)%,(23.55±0.11)%,(62.78±1.42)%,(87.53±0.27)% respectively,and for 48h the inhibitive rates increased to(30.40±0.68)%,(46.18±1.80)%,(89.77±0.21)%,(97.94±0.18)% in MKN-45 respectively(P0.05).The apoptotic rates were(25.5±2.66)% and(57.23±2.19)% in MKN-45 after treatment with celecoxib(50,100μmol/L) for 24h.Correspondingly,the apoptotic peaks were observed by FCM at these two concentrations.In addition,it was observed that celecoxib could decrease the expression of Bcl-2,but promoted the expression of Bax protein.The apoptotic morphology,such as karyopycnosis and apoptotic body,could be observed by TEM in celecoxib groups.The 50μmol/L and 100μmol/L celecoxib groups produced characteristic DNA ladder on DNA gel,but not in the control.Conclusion:Celecoxib could inhibit the proliferation and induce the apoptosis of the MKN-45 cells in a dose-and time-dependent way.The possible mechanism may be celecoxib could reduce the expression of Bcl-2 and increase the expression of Bax.