PI3K/mTOR双重抑制剂PF-04691502诱导人胃癌SGC-7901细胞凋亡

 目的：检测PI3K/mTOR双重抑制剂PF-04691502对人胃癌SGC-7901细胞增殖和凋亡的影响及可能的分子机制。方法：MTT法检测细胞活力；流式细胞术分析细胞周期变化；Annexin V-FITC/PI双标法测定细胞凋亡；免疫印迹分析细胞内蛋白表达的变化。结果：PF-04691502处理SGC-7901细胞后，降低细胞的活力并促进细胞阻滞于G1期，同时抑制cyclin D1的表达并上调p21的蛋白水平。PF-04691502可明显诱导SGC-7901细胞凋亡，其机制与其促进caspase家族成员的活化并切割聚（腺苷二磷酸核糖）聚合酶［poly(ADP-ribose)polymerase, PARP］ 底物密切相关。结论：PI3K/mTOR 双重抑制剂PF-04691502能够通过阻滞细胞周期来抑制SGC-7901细胞的增殖，同时能够激活细胞内caspase，使PARP发生剪切而诱导细胞凋亡。

PI3K/mTOR dual inhibitor PF-04691502 induces apoptosis of human gastric cancer SGC-7901 cells

AIM:To determine the antitumor effect of PF-04691502, a dual inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt and mammalian target of rapamycin (mTOR), on the viability and apoptosis of human gastric cancer cell line SGC-7901.METHODS:Cell viability was analyzed by MTT assay. Cell cycle was detected by flow cytometry, and Annexin V-FITC/PI dual staining was used to detect cell apoptosis. Protein expression of p21, cyclin D1, caspase-3, caspase-8, caspase-9 and poly(ADP-ribose) polymerase (PARP) was determined by Western blotting. RESULTS:MTT assay and cell cycle analysis results indicated that PF-04691502 inhibited the viability of SGC-7901 cells in a dose-dependent manner, and arrested the cells in G1 phase. PF-04691502 down-regulated the expression of cyclin D1 and up-regulated the expression of p21. In addition, SGC-7901 cells treated with PF-04691502 showed typical characteristics of apoptosis, accompanied by activation of caspases and cleavage of PARP. CONCLUSION: The PI3K/mTOR dual inhibitor PF-04691502 induces the apoptosis and inhibited the growth of SGC-7901 cells, implicating its potential therapeutic value for the treatment of cancer.