曲古菌素A对乳腺癌MDA-MB-231细胞的作用  

The investigation of effect of trichostatin A to breast cancer MDA-MB-231 cell line

作　　者：姜小良[1] 张徽[1] 刘香丽[1] 林晓[1] 

机构地区：[1]重庆医科大学基础医学院病理学教研室,重庆400016

出　　处：《重庆医科大学学报》2008年第3期312-316,共5页Journal of Chongqing Medical University

摘　　要：目的:研究组蛋白去乙酰化酶(Histone deacetylase,HDAC)抑制剂曲古抑菌素A(Trichostatin A,TSA)对乳腺癌细胞MDA-MB-231增殖、侵袭、细胞周期及ERα表达的影响。方法:100～400nmol/L的TSA分别处理MDA-MB-231细胞6～48h后用四甲基偶氮唑蓝比色法(MTT法)检测MDA-MB-231细胞的生长活性。应用流式细胞仪观察细胞周期的变化。采用RT -PCR法检测MDA-MB-231细胞在24h不同浓度100～400nmoi/L TSA作用下对ERα,MMP-9 mRNA表达的影响。采用免疫组织化学法检测MDA-MB-231细胞在24h不同浓度100～400nmol/L TSA作用下对ERα,MMP-9在细胞中表达的影响。采用细胞侵袭实验检测MDA-MB-231细胞在24h不同浓度100～400nmol/L TSA作用下细胞侵袭力的变化。结果:TSA可显著抑制MDA-MB-231细胞的增殖,呈时间及剂量依赖性。TSA能够延缓细胞周期G_2/M期进程,阻滞细胞于G_2期。RT-PCR显示,TSA能够上调ERαmRNA在MDA-MB-231细胞中的表达,下调MMP-9在MDA-MB-231细胞中的表达。侵袭实验显示TSA能够较明显的抑制MDA-MB-231细胞的侵袭。结论:TSA能够较明显的上调ERα与下调MMP-9的表达可能是抑制MDA-MB-231细胞增生侵袭与转移的重要机制之一。Objective：To investigate the influence of histone deacetylase inhibitor（Trichostatin A） to multiplication, invasion, cell cycle of breast cancer MDA-MB-231 cell line. Methods：Mter 6-48hours treatment with the concentration（100-400nmol/L）of Trichostatin,the growth activity of MDA-MB-231 cell line was detected by MTT. The expression of ERα ,MMP-9 mRNA was detected by RT-PCR with different concentration（100-400nmol/L TSA） during 24 hours to MDA-MB-231 cell line. The expression of ERa, MMP-9 protein was examined by immunohistochemistry with different concentration（ 100 - 400nmol/L TSA） during 24 hours treatment to MDA-MB-231 cell hne. With cell invasion experiment to detect the change of invasive power by using different concentration（100-400nmol/L TSA） during 24 hours to MDA-MB-231 cell line. Results： Trichostatin can inhibit the growth of MDA-MB-231 cell line,which was time and dose dependent. Trichostatin can delay the cell cycle G2/M stage,stop the cell stage in G2 stage. Trichostatin can up-regulate the expression of ERα mRNA, down-regulate the expression of MMP-9 mRNA in cells. The invasion experiment indicate that Trichostatin can conspicuous inhibit the invasion of MDA-MB-231 cell line. Conclusions：Trichostatin can inhibit the accrementition, invasion and metastasis of MDA-MB-231 cell line evidently,and one of the mechanism may be the up-regulation of ERα and the down-regulation of MMP-9.

关 键 词：曲古抑菌素A(TSA) MDA—MB-231细胞 雌激素受体α(ERα) 基质金属蛋白酶9(MMP-9) 

分 类 号：R737.9[医药卫生—肿瘤]