LY294002对胃癌细胞的抑制作用

Inhibitory effect of LY294002 on gastric cancer

目的探讨PI3K/Akt途径特异抑制剂LY294002对胃癌细胞化疗药物敏感性的作用。方法噻唑蓝(MTT)比色法测定单独或联用LY294002时化疗药物在体外对胃癌细胞的抑制作用,流式细胞术检测胃癌细胞的凋亡率及细胞内多柔比星的蓄积和潴留,Western印迹检测胃癌细胞中Bcl-2蛋白的表达。结果长春新碱、多柔比星、丝裂霉素联用LY294002实验组与单独药物组相比,其IC50值均明显降低(P<0.05),细胞凋亡率明显增高,而细胞内Bcl-2蛋白表达则明显降低。结论LY294002能有效提高化疗药物对胃癌细胞的抑制作用。

Objective To investigate whether LY294002, a PI3K/Akt signaling pathway specific inhibitor, increases the sensitivity of gastric cancer to anticancer chemotherapeutic agents. Methods Sensitivity of gastric cancer cells to chemotherapeutic agents was evaluated by in vitro MTT assay in the absence or presence of LY294002. Apoptosis of the cells was examined with Annexin V/PI staining. Adriamycin accumulation and retention in cells were determined by flow cytometric analysis. Expression of Bcl-2 protein was detected by Western blotting. Results When SGC7901 ceils were treated with chemotherapeutic agents in combination with LY294002, the IC50 values for adriamycin, vincristine or mitomycin significantly decreased with the increasing concentrations of LY294002 compared with those that were treated only with chemotherapeutic agents（P〈0.05）. Flow cytometric analysis showed that LY294002 significantly increased vincristine-induced apoptosis and adriamycin accumulation and retention（P〈0.05）.Westem blotting showed that the Bcl-2 expression level was significantly lower in LY294002-treated than in untreated SGC7901 cells. Conclusion LY294002 can effectively increase the inhibitory effects of anticancer chemotherapeutic agents on gastric cancer cells.