选择性COX-2抑制剂Celecoxib对胃癌细胞增殖影响的探讨

Effect of Selective Cyclooxygenase-2 Inhibitor Celecoxib on Proliferation of Gastric Cancer Cell

目的:探讨选择性COX-2抑制剂Celecoxib对胃癌SGC-7901细胞增殖和凋亡的影响。方法:应用MTT法和FCM检测Celecoxib对胃癌SGC-7901细胞增殖、细胞凋亡、细胞周期和COX-2蛋白和bcl-2蛋白表达的影响。结果:Celecoxib呈时间、剂量依赖性抑制胃癌SGC-7901细胞生长,72h细胞最高存活率为48.7%,最低为20.5%;COX-2蛋白含量由26.73±0.06降至5.79±1.44,bcl-2蛋白含量由2.76±0.14降至0.78±0.05,COX-2蛋白和bcl-2蛋白表达的降低呈浓度依赖性;随着药物浓度的增高,细胞凋亡率由3.0%增加到33.0%;G0/G1期细胞比例增加到(87.29±1.34)%,S期和G2/M期细胞比例分别降低到(8.91±0.78)%、(3.80±0.55)%。结论:Celecoxib能够诱导胃癌SGC-7901细胞的凋亡,影响细胞周期的分布,从而有效地抑制胃癌SGC-7901细胞的增殖;Celecoxib诱导胃癌SGC-7901细胞的凋亡可能主要通过抑制COX-2的生物活性来实现,并与bcl-2蛋白表达的下调有关。

Objective: To study the the effect of selective COX-2 inhibitor Celecoxib on proliferation and apoptosis of gastric cancer cell. Methods: Investigate the effect of Celecoxib on proliferation of gastric cancer cell line SGC-7901 by MTT assay. Detect the change of apoptosis, cell cycle and the expression of COX-2, bcl-2 protein using flow cytometry analysis. Results: Celecoxib could inhibit the proliferation of SGC-7901 cell and showed a time-and dose-dependent manner. The highest survival rate of SGC-7901 cell is 48.7% and the lowest is 20.5% after 72 hour of Celecoxib action. The content of COX-2 and bcl-2 protein was decreased from 26.73±0.06 to 5.79±1.44, from 2.76±0.14 to 0.78±0.05 respectively. The decrease of them showed a dose-dependent manner. The apoptosis rate of the cell increased from 3% to 33% with the raise of Celecoxib concentration. The percentage of cell in G0/G1 phase increased to 87.29±1.34% and the percentage of cell in S and G2/M phase reduced to 8.91±0.78%, 3.80±0.55%, respectively. Conclusions: Celecoxib could inhibit the proliferation of SGC-7901 cell effectively through inducing apoptosis and influencing the distribution of cell cycle of SGC-7901 cell. The mechanism of Celecoxib induced apoptosis of SGC-7901 cell mainly through inhibit the biological activity of COX-2 and may associated with the down-regulation of bcl-2 protein.