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

作　　者：刘登辉[1] 刘红光[1] 康颖[2] 蒋静[1] 佘键涛[1] 文波[1] 赵茂勋[1] 王雄宇[1] 

机构地区：[1]南华大学附属第一医院肿瘤外科,湖南衡阳421001 [2]南华大学外科学教研室,湖南衡阳421001

出　　处：《现代生物医学进展》2013年第8期1430-1434,共5页Progress in Modern Biomedicine

基　　金：湖南省卫生厅一般项目(B2010-039)

摘　　要：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.

关 键 词：乳腺癌 2-甲氧基雌二醇 缺氧诱导因子-1Α CXCR4 血管内皮生长因子 肿瘤侵袭转移 

分 类 号：R739.9[医药卫生—肿瘤]