缺氧条件下大豆异黄酮对胃癌细胞增殖和缺氧诱导因子-1α表达的影响

目的:研究缺氧条件下大豆异黄酮(soy bean isoflavone,SI)对人胃癌细胞株SGC-7901生长抑制作用及可能机制。方法:运用产气袋法(GasPaK)制造缺氧条件,实验分为正常对照、SI、缺氧对照和缺氧SI四组,用MTT法检测常氧和缺氧条件下药物效应。流式细胞仪分析各组细胞周期分布,透射电镜观察细胞超微形态的改变,免疫细胞化学法检测各组细胞缺氧诱导因子HIF-1α和FAS的表达。结果:不同浓度SI在常氧和缺氧条件下都对人胃癌细胞株SGC-7901生长有抑制作用,并呈剂量-效应关系,细胞均滞留于G2/M期,缺氧条件下SI组抑制作用增加,细胞凋亡率增加。透射电镜观察常氧下SI处理后细胞出现凋亡,缺氧条件下出现凋亡和坏死。SI在不同氧条件下均上调Fas表达,并能下调因缺氧表达增加的HIF-1。结论:SI对人胃癌细胞生长有抑制作用,其机制可能通过阻抑细胞周期进程,上调FAS蛋白表达,从而诱导胃癌细胞凋亡而实现的。缺氧条件下SI抑制作用增强,抑制HIF-1α的表达可能是其重要机制。

EFFECT OF SOYBEAN ISOFLAVONE ON PROLIFERATION AND EXPRESSION OF HIF-1αIN GASTRIC CANCER CELL SGC-7901 DURING HYPOXIA

Objetive: To study the effect of soybean isoflavone(SI) on the growth of gastric cancer cell SGC-7901 during hypoxia and its mechanisms. Method: The environment of hypoxia was established by GasPaK method. The effect of SI was determined by MTT and FCM which was used for studying apoptosis and cell cycle of SGC-7901. Electron microscopy was used to study the effects of SI on apoptosis and necrosis of SGC-7901. Cell-immunochemistry was used to observe the change of hypoxia-inducible factor HIF-1α and FAS expression. Results: SI could inhibit significantly the growth of SGC-7901, and arrest the cell in G2/M phases during normal and hypoxia environment. The inhibitory effect was elevated significantly during hypoxia. Electron microscopy showed the cell apoptosis and necrosis. FAS expression was elevated by SI during normal and hypoxia environment, and HIF-1α expression was downregulated during hypoxia. Conclusion: SI can inhibit SGC-7901 cell growth via arrest of cell cycle, elevated expression of FAS, apoptosis and necrosis induction and other pathways. The inhibition of the increased HIF-1α expression is probably the mechanism of the inhibitory effects of SI during hypoxia.