苯并二氢吡喃衍生物对人类乳腺癌细胞增殖的影响  

Effect of xy2004, a centchroman derivative, on proliferation of MCF-7 cells in vitro and the mechanism

作　　者：侯进[1] 李萍[1] 曾菊绒[1] 胥晓丽[1] 熊晓云 弥曼[1] 

机构地区：[1]西安医学院基础医学部药理学与毒理学教研室,陕西西安710068 [2]西安利君制药有限责任公司,陕西西安710077

出　　处：《南方医科大学学报》2014年第10期1511-1514,共4页Journal of Southern Medical University

基　　金：国家自然科学基金(F050903);国家863资助项目(2004AA2Z3480);陕西省教育厅专项科研项目(2010JK805);西安医学院博士科研启动基金(2011DOC04);西安医学院扶植基金(2009FZ2)~~

摘　　要：目的研究苯并二氢吡喃衍生物xy2004对乳腺癌细胞增殖的影响。方法采用MTT比色法测定化合物对MCF-7细胞的增殖作用;用流式细胞术测定化合物对细胞凋亡的影响,用放射性配体结合法考察化合物与雌激素受体(ER)的亲和力,用蛋白印记杂交法观察细胞内凋亡蛋白的变化。结果低浓度的xy2004促进MCF-7细胞增殖,其增殖作用可被tamoxifen阻断;高浓度xy2004抑制MCF-7细胞增殖,诱导细胞凋亡,Bax蛋白表达增强,Bcl-2蛋白表达降低;xy2004对ERα和ERβ的IC50分别为7.38×10-5mol/L和4.12×10-7mol/L。结论化合物xy2004低浓度促进MCF-7细胞增殖,其增殖作用机制与ERα激动有关,高浓度抑制MCF-7细胞增殖,抗增殖作用与诱导细胞凋亡相关。Objective To investigate the effect of xy2004, a centchroman derivative, on the proliferation of MCF-7 cells and the mechanisms. Methods The effects of xy2004 on MCF-7 cell proliferation and apoptosis were evaluated with MTT assay and flow cytometry, respectively. The expressions of the apoptosis- related proteins were examined with Western blotting.Competitive estrogen-receptor binding assay was used to investigate the affinity of xy2004 to estrogen receptors（ER）. Results xy2004 induced proliferation of MCF-7 cells at low concentrations but inhibited cell proliferation at high concentrations. The application of tamoxifen inhibited xy2004-induced proliferation of MCF-7 cells. The relative binding affinity of xy9906 to ERαand ERβ, presented as the IC50 value, was 7.38×10- 5mol/L and 4.12×10- 7mol/L, respectively. Treatment of MCF-7 cells with high-concentration xy2004 reduced the cellular expression of Bcl-2 protein and increased Bax protein expression. Conclusion At low concentrations, xy2004 directly stimulates the proliferation of MCF- 7 cells through ligand- receptor binding, and at high concentrations, it inhibits the cell proliferation by regulating the expression levels of the apoptosis-related proteins.

关 键 词：苯并二氢吡喃 MCF-7细胞 雌激素受体 增殖 

分 类 号：R737.9[医药卫生—肿瘤]