尼美舒利抑制胃癌细胞蛋白激酶B活性的研究

Nimesulide,a selective cyclooxygenase-2 inhibitor inhibits telomerase activity by blocking activation of PKB in gastric cancer cell line

目的 观察选择性环氧化酶 2 (COX 2 )抑制剂尼美舒利对胃癌细胞株SGC790 1增殖、端粒酶活性和蛋白激酶 (PKB)的影响 ,以探讨其抗肿瘤作用机制。方法 尼美舒利作用胃癌细胞株SGC790 1不同时间后 ,采用噻唑蓝 (MTT)比色法和PCR ELISA半定量法检测细胞的生存率和端粒酶活性 ,PKB活性的检测采用非放射性蛋白激酶活性分析法。结果 尼美舒利抑制SGC790 1细胞的生长呈时间 剂量依赖性 ,同时它也显著抑制SGC790 1细胞的端粒酶和PKB活性 ,且端粒酶活性的降低与PKB活性的抑制有关。结论 选择性COX 2抑制剂能抑制胃癌细胞株的端粒酶活性 ,其作用机制可能与阻碍PKB的活性有关 ,这可能是选择性COX 2抑制剂抗肿瘤的又一新的机制。

Objective To study the effects of nimesulide,a selective COX-2 inhibitor,on cell viability,telomerase and PKB activities in human gastric cancer cell line SGC7901 and to explore its molecular mechanism of selective growth inhibition. Methods MTT assay was used to determine cell viability after incubation for 0,12,24,and 48 h in different concentrations (0,25,50,100,200 μmol/L) of nimesulide and /or okadaic acid (300 nmol/L). Telomerase and protein kinase B (PKB) activities were detected using TRAP PCR-ELISA and nonradioactive IP-kinase assay. Results Nimsulide caused a time and dose-dependent reduction of cell numbers of SGC7901. The telomerase and PKB activities were significantly inhibited,and the inhibition of telomerase activity was partly associated with decrease in PKB activity. Conclusion Selective COX-2 inhibitor nimesulide inhibits telomerase activity of gastric cancer cells by partly blocking the activation of protein kinase B. The results suggest an additional signaling pathway underlying the anti-cancer effect of COX-2 inhibitor.