摘要
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。
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 viabiIity of SGC-7901 cells in a dose-depend- ent 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.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2013年第11期1962-1965,共4页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81272683)
山东省自然科学基金资助项目(No.ZR2011HQ034)
