2-甲氧基雌二醇对乳腺癌MCF-7细胞HIF-1α、CXCR4、VEGF表达的影响

Effects of 2-Methoxyestradiol on Expressions of mRNAs and Proteins of HIF-1α, CXCR4, VEGF in Human Breast Cancer MCF-7 Cells

目的:探讨2-甲氧基雌二醇(2-Methoxyestradiol,2ME2)对乳腺癌MCF-7细胞生长及缺氧诱导因子-1α(Hypoxia-induciblefactor1α,HIF-1α)、趋化因子受体-4(CXC chemokine receptor-4,CXCR4)、血管内皮生长因子(Vascular endothelial growth factor,VEGF)表达的影响。方法:采用MTT法检测不同浓度2ME2对MCF-7细胞的增殖抑制作用;Hoechest 33258染色观察细胞凋亡形态学改变;RT-PCR、Western blot分别检测不同浓度2ME2对乳腺癌MCF-7细胞中HIF-1α、CXCR4、VEGF mRNA及蛋白表达水平的影响。结果:2ME2可较强的抑制MCF-7细胞增殖,并呈时间和剂量依赖性;经2ME2作用48h后MCF-7细胞表现出典型的凋亡形态特征;不同浓度2ME2作用于MCF-7细胞48小时后,随着药物浓度的增加细胞中HIF-1α、CXCR4、VEGF在mRNA及蛋白表达水平逐渐降低,与对照组相比有统计学意义(P<0.05)。结论:2ME2可通过降低HIF-1α、CXCR4、VEGFmRNA及蛋白表达,抑制乳腺癌MCF-7细胞的增殖及肿瘤血管生成和侵袭转移相关因子的表达。

Objective： To investigate the effects of 2-Methoxyestradiol （2ME2） on expressions of mRNAs and proteins of hypoxia-inducible factor 1α（HIF-1α）, cxc chemokine receptor-4（CXCR4） and vascular endothelial growth factor（VEGF） in human breast cancer MCF-7 cells. Methods： The inhibitory effect of 2ME2 on proliferation of human breast cancer MCF-7 cells was evaluated by the MTT assay, and the apoptotic effect was demonstrated by Hoechst 33258 staining; RT-PCR and western blotting were employed to measure the expressions ofHIF-la, CXCR4 and VEGF mRNAs and proteins of the cells respectively. Results： 2ME2 could significantly inhibit the proliferation of human breast cancer MCF-7 cells in a dose-dependent and time-dependent effects; The cells treated with 2ME2 showed typical morphological change of apoptosis; With the increasing concentration of 2ME2 for 48h, the expressions of HIF-lot, CXCR4 and VEGF mRNAs and proteins of MCF-7 cells reduced gradually, which had statistical significance compared with the control group （P〈0.05）. Conclusion： 2ME2 can inhibit proliferation and induce apoptosis of human breast cancer MCF-7 cells in vitro through down-regnlating HIF-1 α CXCR4 and VEGF, which correlated tumor angiogenesis, invasion, metastasis and so on.