恩度对雌激素受体阳性的人乳腺癌细胞生长的抑制作用及其分子机制的研究  

Inhibitory Effects of Endostar against the Growth of Estrogen Receptor-Positive Breast Cancer Cells and the Molecular Mechanisms of Action

作　　者：孙富家[1] 刘欣[1] 陈林林[1] 刘昆[1] 姜静 张国营[1] 

机构地区：[1]烟台大学药学院,山东烟台264005 [2]先声烟台麦得津生物制药有限公司

出　　处：《烟台大学学报（自然科学与工程版）》2013年第2期123-130,共8页Journal of Yantai University(Natural Science and Engineering Edition)

基　　金：国家科技部十二五"863"课题资助项目(2012AA020206);国家自然科学基金资助项目(30973553/C180105);山东省科技攻关项目(2009GG10002087);山东省自然科学基金资助项目(ZR2012HM016)

摘　　要：研究了重组人血管内皮抑素(恩度)对雌激素受体阳性的人乳腺癌MCF-7细胞株生长的抑制作用与其分子机制.采用MTT法、台盼蓝染色法和中性红染色法检测不同浓度恩度对MCF-7细胞生长的抑制作用,Hoechst33258荧光染色法和TUNEL分析法观察恩度诱导MCF-7细胞凋亡的形态变化,蛋白印迹法检测恩度作用的MCF-7细胞中与生长和凋亡相关蛋白的表达.结果表明,恩度显著性地抑制MCF-7细胞的生长并诱导细胞凋亡.此外,恩度显著性地减少MCF-7细胞VEGFR1,c-Met,ERα,Akt,NF-κB,Bcl-2和CyclinD1蛋白的表达,明显地上调Bax蛋白的表达,其作用的分子机制可能是通过抑制VEGFR1/c-Met/ERα-Akt-NF-κB信号传导通路,下调Bcl-2/Bax蛋白比率、降低CyclinD1蛋白的水平.The effects of recombinant human endostatin Endostar on cell growth of estrogen receptor-positive human breast cancer MCF-7 cell line and the molecular mechanisms of action are investigated. The growth inhibition of MCF-7 cells by different concentrations of Endostar is evaluated using MTT, Trypan Blue staining and Neutral Red tests. The Endostar-induced apoptotic morphological changes in MCF-7 cells are detected using Hoechst 33258 stai- ning and TUNEL assay. The protein expressions related to the growth and apoptosis in MCF-7 cells treated with En- dostar are analyzed using Western blotting. The results show that Endostar significantly suppresses the growth of the MCF-7 cells and induces the apoptosis in MCF-7 cells. In addition, Endostor remarkably reduces the protein expressions of VEGFR1, c-Met, ERα, Akt, NF-κB, Bcl-2 and CyelinD1. It also markedly enhances the protein expressions of Bax in MCF-7 cells. The molecular mechanism of action may be related to the down-regulation of Bel- 2/Bax and Cyclin D1 protein expressions via inhibiting the signaling pathways of VEGFR1/c-Met/ERα-Akt-NF-κB in MCF-7 cells.

关 键 词：恩度 人乳腺癌 生长抑制和凋亡 VEGFR1 c—Met ER仅-Akt—NF—κB信号传导 

分 类 号：R971[医药卫生—药品]