HER2介导乳腺癌细胞多药耐药的作用及机制  

The HER2-mediated multidrug resistance mechanism in breast cancer cell line

作　　者：丁渭[1] 郑春艳[1] 贺智敏[1] 吕辉[1] 刘孝荣[1] 余艳辉[1] 陈主初[1] 

机构地区：[1]中南大学湘雅医学院肿瘤研究所,湖南长沙410078

出　　处：《国际病理科学与临床杂志》2005年第5期381-385,共5页Journal of International Pathology and Clinical Medicine

基　　金：国家自然科学基金重点项目(20335020);湖南省卫生厅重点课题(Z02-01)

摘　　要：目的筛选HER2高表达乳腺癌细胞化疗耐受的药物种类,探讨HER2介导的乳腺癌多药耐药的机制。方法构建HER2稳定高表达的乳腺癌细胞MCF-7/HER2模型;MTT法检测该细胞对多种临床常用的抗乳腺癌药物的敏感性;Hochest33258染色观察药物诱导的MCF-7/HER2的凋亡率,并采用聚合酶链式反应(RT-PCR)检测细胞中bcl-2和survivin基因的mRNA表达。结果MCF-7/HER2细胞对Taxol,MMC,5-FU,VP-16及TSPA的耐药指数分别为对照细胞的74,22,2.5,3.5和2.8倍,出现了明显的药物抗性(P<0.05);而对CDDP,ADM,VBL,VCR,NBV和MTX等的耐药指数与对照组相比,差异无统计学意义(P>0.05);由Taxol,MMC,5-FU,VP-16诱导的MCF-7/HER2细胞凋亡率明显低于对照细胞;MCF-7/HER2细胞survivin基因表达明显高于对照组,而bcl-2基因表达与对照组比较,差异无统计学意义。结论HER2可介导乳腺癌细胞对Taxol,MMC,5-FU,VP-16和TSPA等的多药抗性,这种多药抗性的产生可能与HER2上调survivin表达所致的凋亡抗性有关。Objective To filtrate the chemoresistance agents of HER2-overexpressing breast cancer cell and to investigate the molecular mechanisms of HER2-mediated multidrug resistance. Methods To set up a breast cancer cell line in which HER2 is overexpressed stably ;the chemosensitivity of anticancer agents in breast cancer cell was defined by MTT assay;Hochest 33258 staining was used to de- tect apoptosis ratio of MCF-7/HER2 and the parental cell induced by chemotherapeutic agents;The mRNA levels of bcl-2 and survivin were analyzed by reverse transcription-polymerose chain reaction（ RT-PCR ）. Results The resistance index of the MCF-7/HER2 to Taxol, MMC, 5-FU, VP-16 and TSPA induced were 74,22,2.5,3.5,2.8 times than that in control, respectively （P〈0.05） ; However, the resistance index to CDDP, ADM, VBL, VCR, NBV, MTX did not show significant difference （ P〉0.05 ） ; the apoptosis ratio of MCF-7/HER2 is lower significantly than vector cells induced by Taxol, MMC, 5- FU, VP-16; RT-PCR results showed the expression of survivin was increased in MCF-7/HER2 cells compared with that in control cells; whereas bcl-2 expression has little alteration between the two groups. Conclusion HER2 is resistant to chemotherapeutic agents 5-FU, MMC, Taxol, VP-16 and TSPA in breast cancer cells; This suggests the chemoresistance mechanisms may be involved in up-regnlating the expression of survivin by HER2.

关 键 词：乳腺癌 表皮生长因子受体2 存活素 药物耐受性 

分 类 号：R737.9[医药卫生—肿瘤] R979.1[医药卫生—临床医学]