Geldanamycin对HER2/neu高表达人乳腺癌细胞系SKBr3增殖及迁移能力的影响  

Geldanamycin inhibits proliferation and motility of human HER2/neu-overexpressing breast cancer cell line SKBr3

作　　者：王珂[1] 马清涌[2] 任予[1] 何建军[1] 陈武科[1] 

机构地区：[1]西安交通大学医学院第一附属医院肿瘤外科,陕西西安710061 [2]西安交通大学医学院第一附属医院肝胆外科,陕西西安710061

出　　处：《南方医科大学学报》2007年第10期1480-1484,共5页Journal of Southern Medical University

基　　金：环境与疾病相关基因教育部重点实验室开放基金(KFJJ-2005-05)

摘　　要：目的探讨Hsp90抑制剂苯醌安莎霉素类抗生素(GA)对HER2/neu高表达人乳腺癌细胞系SKBr3增殖及迁移能力的影响。方法用Western蛋白印迹法检测GA介导的HER2/neu酪氨酸激酶的降解;MTT法分析GA对肿瘤细胞存活率的影响;流式细胞仪测定GA对肿瘤细胞周期的影响;RT-PCR和real-time PCR分析GA对cyclin D1表达的影响以及分析GA对肿瘤细胞迁移能力的干预作用。结果GA以剂量/时间依赖性的方式降解了HER2/neu酪氨酸激酶的表达并抑制了SKBr3乳腺癌细胞的增殖,这种增殖抑制效应表现在:GA干预后乳腺癌细胞的存活率明显降低;GA阻断了乳腺癌细胞细胞周期的进展,使细胞周期停滞于G1期,而这两种表现与cyclin D1表达量的减低有着明显的关系。GA的干预也同时降低了肿瘤细胞的迁移能力。结论本研究证实GA能够降解HER2/neu酪氨酸激酶并抑制HER2/neu高表达人乳腺癌细胞系SKBr3的增殖和迁移能力。Objective To investigate the antitumor effect of a benzoquinone ansamycin antibiotic, geldanamycin （GA）, against HER2/neu tyrosine kinase-overexpressing human breast cancer cell line SKBr3. Methods To evaluate the antitumor activity of GA, the degradation of HER2/neu tyrosine kinase in GA-treated SKBr3 cells was analyzed by Western blotting, their proliferation assessed using MTT assay, and the cell cycle distribution identified by flow cytometry. RT-PCR and Real-time PCR were employed to detect cyclin D1 mRNA expression and cell culture inserts model was used to evaluate the motility of the cells. Results GA induced a dose- and time-dependent degradation of HER2/neu tyrosine kinase and cell proliferation inhibition. GA treatment obviously decreased the survival rates of the cancer cells, leading also to a dose-dependent G1 arrest. The antitumor effects of GA proved to be relevant with declined transcription of cyclin D1. The GA-treated cells also exhibited reduced motility. Conclusion GA can efficiently destabilize HER2/neu tyrosine kinase and inhibit the proliferation and motility of human breast cancer cell line SKBr3 overexpressing HER2/neu tyrosine kinase.

关 键 词：HER-2/NEU GELDANAMYCIN CYCLIN D1 乳腺癌 

分 类 号：R737.9[医药卫生—肿瘤]