PPARγ通路在舒林酸抑制胃癌细胞增殖中作用及机制.docVIP

PPARγ通路在舒林酸抑制胃癌细胞增殖中作用及机制 　 作者：吴克俭，费素娟，刘军权，陈复兴 【摘要】 目的 了解舒林酸是否通过过氧化物酶增殖物激活受体γ（PPARγ）途径影响人胃癌SGC- 7901细胞的增殖，初步探讨PPARγ途径在舒林酸抗肿瘤作用中的机制。方法 培养人胃癌SGC-7901 细胞，经特异的PPARγ抑制剂GW9662作用，采用四甲基偶氮唑蓝比色法（MTT法）检测舒林酸对细胞增殖的影响及用免疫细胞化学法检测PPARγ、Bcl-2、Bax蛋白表达。结果 MTT法显示GW9662作用后，舒林酸对SGC-7901细胞增殖的抑制作用减弱，细胞增殖增多，而且这种作用在一定范围内呈剂量和浓度依赖性；免疫细胞化学法显示GW9662预先干预与舒林酸单独作用相比，SGC7901细胞的PPAR-γ蛋白表达明显减少， Bax的表达亦明显降低，而Bcl-2蛋白表达增强(Plt;0.01) 。结论 PPARγ途径在舒林酸抗肿瘤作用中具有一定作用，其机制与激活PPARγ对Bcl-2、Bax蛋白的表达有关。 【关键词】 舒林酸；人胃癌SGC- 7901细胞；PPARγ通路；GW9662； Bcl-2；Bax 　　Abstract： Objective To investigate the effect of sulindac on the proliferation of human gastric cancer cell line SGC-7901 and its antineoplastic mechanism via the PPARγ pathway, so as to make a preliminary probe into the mechanism of the PPARγ pathway in the antineoplastic effect of sulindac. Methods Cultured human gastric cancer cell line SGC-7901 was treated by the specific PPARγ inhibitor GW9662, followed by detection of the effect of sulindac on the proliferation of SGC7901 cells by MTT assay and determination of the expressions of PPARγ, Bcl-2 and Bax protein by immunocytochemical method, respectively. Results MTT assay showed that the inhibitory effect of sulindac on human gastric cancer SGC7901 cells was attenuated subsequent to GW9662 treatment, with an increase in cell proliferation and in a dose-concentration dependence manner within a certain range. Meanwhile, the immunocytochemical result showed that with GW9662 pre-intervention in sulindac, compared with sulindac administration alone, the expression of PPAR-γ protein was obviously reduced, so was the Bax expression, while the expression of Bcl-2 was enhanced (Plt;0.01). Conclusion PPARγ pathway has certain role to play in the anti-tumor effect of sulindac, and the underlying mechanism is involved in the activation of PPARγ, the up-regulation of Bcl-2 expression and down-regulation of Bax protein expression. Key words: sulindac; human gastric tumor SGC-7901; PPARγ pathway; GW9662; Bcl-2; Bax 既往认为非甾体类抗