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作 者:郭花[1] 朱金水[1] 张强[1] 王红建[1] 王龙[1]
机构地区:[1]上海交通大学第六人民医院消化内科,上海200233
出 处:《上海交通大学学报(医学版)》2009年第4期374-377,共4页Journal of Shanghai Jiao tong University:Medical Science
摘 要:目的探讨低氧环境下PI3K抑制剂2-(4-吗啉基)-8-苯基-4氢-1-苯并吡喃-4-酮(LY294002)对人胃癌SGC-7901细胞中磷脂酰肌醇3-激酶(PI3K)/丝氨酸苏氨酸激酶(Akt)信号通路、细胞生长、细胞凋亡及低氧诱导因子-1α(HIF-1α)mRNA表达的影响。方法应用LY294002作用于低氧环境中的人胃癌SGC-7901细胞(低氧+LY294002组),采用CCK-8试剂盒检测SGC-7901细胞生长;流式细胞仪检测细胞凋亡百分比;Western blotting检测P13K和p-Akt蛋白表达;RT—PCR检测HIF-1α mRNA表达。以低氧环境中未加LY294002的细胞作为对照(低氧组)。结果LY294002能抑制低氧环境中SGC-7901细胞增殖,抑制效果在药物作用后第2~6天时最为明显(P〈0.05),低氧+LY294002组中细胞凋亡百分比明显高于低氧组(P〈0.01)。LY294002能明显抑制PI3K、p-Akt蛋白以及HIF-1α mRNA的表达,与低氧组比较差异均有统计学意义(P〈0.05)。结论LY294002能抑制低氧环境中人胃癌SGC-7901细胞生长,促进细胞凋亡,抑制PI3K/Akt信号通路及其下游HIF-1α mRNA的表达。Objective To investigate the effects of PI3K inhibitor (LY294002) on PI3K/Akt signal pathway, cell growth, cell apoptosis and expression of hypoxia inducible factor (HIF)-1α mRNA in human gastric carcinoma SGC-7901 cells in hypoxia enviroment. Methods Human gastric carcinoma SGC-7901 cells in hypoxia enviroment were treated with LY294002 (hypoxia + LY294002 group). CCK-8 kit was applied to evaluate the growth of SGC-7901 cells, flow cytometry was adopted to determine the cell apoptosis rate, Western blotting was employed to detect the expression of PI3K and p-Akt protein, and RT-PCR was used to detect the expression of HIF-1α mRNA. SGC-7901 cells in hypoxia enviroment without LY294002 were served as control (hypoxia group). Results LY294002 inhibited the growth of SGC-7901 cells in hypoxia environment, and the inhibition effect was most significant from d2 to d6 after treatment (P 〈0.05). Cell apoptosis rate in hypoxia + LY294002 group was significantly higher than that in hypoxia group (P 〈 0.01 ). LY294002 inhibited the expression of PI3K, p-Akt protein and HIF-1α mRNA, and the difference was significant when compared with hypoxia group ( P 〈 0.05). Conclusion LY294002 could inhibit the growth of SGC-7901 cells, increase cell apoptosis, and inhibit PI3K/Akt signal pathway and HIF-1α mRNA expression in hypoxia environment.
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