环氧合酶-2特异抑制剂诱导胃癌细胞凋亡的机制研究

Mechanism of apoptosis induced by specific COX-2 inhibitor SC236 in gastric cancer cells

目的 探讨环氧合酶 - 2 (COX -2 )特异抑制剂SC2 36诱导胃癌细胞凋亡的机制。方法SC2 36处理AGS细胞后 ,吖嘧橙染色观察细胞凋亡 ,免疫印迹法检测凋亡相关蛋白、细胞色素C水平。caspase- 3的激活通过免疫印迹法检测其活性片段、其底物多聚 (ADP 核糖 )聚合酶 (PARP)的裂解和比色法检测其催化活性来确定。结果 SC2 36处理AGS细胞可明显提高前凋亡蛋白Bak的水平 ,促使细胞色素C从线粒体进入胞浆 ,并激活caspase 3。caspase 3的特异抑制剂z DEVD fmk可以抑制SC2 36诱导的凋亡 ,细胞凋亡率由 (33.4± 3.2 ) %下降到 (16 .1± 1.5 ) %。结论 SC2 36至少部分通过上调Bak、促进细胞色素C的释放以及激活caspase 3的途径诱导胃癌细胞凋亡。

Objective To investigate the underlying mechanism of apoptosis inducing effect of a specific COX 2 inhibitor SC236 in gastric cancer cells. Methods Western blot analysis was used to measure apoptosis related proteins, cytochrome c, and caspase 3. The catalytic activity of the caspases was measured using a colorimetric assay. Results Treatment of AGS gastric cancer cells with SC236 caused a significant elevation of the pro apoptotic protein Bak, release of cytochrome c to the cytosol, and activation of caspase 3. A specific caspase 3 inhibitor, z DEVD fmk, blocked SC236 induced apoptosis. Conclusion SC236 inhibits cell growth and induces apoptosis in gastric cancer cells at least partly through the up regulation of Bak, stimulation of cytochrome c release, and activation of caspase 3.