南方医科大学学报2013，Vol.33Issue(1)：44-47,4.DOI:10.3969/j.issn.1673-4254.2013.01.10
siRNA沉默葡萄糖调节蛋白78可增强乳腺癌细胞对顺铂的敏感性
Small interfering RNA-mediated glucose-regulated protein 78 knockdown enhances chemosensitivity of breast cancer cells to cisplatin
摘要
Abstract
Objective To investigate the effect of small interfering RNA-mediated glucose-regulated protein 78 (GRP78) knockdown on the chemosensitivity of breast cancer cells to cisplatin. Methods Human breast cancer cell line MDA-MB-231 was exposed to different doses of cisplatin (0,1, 2, 4, 8, and 16 μmol/L), and the changes in cell viability were detected using MTT assay. PI/Annexin V staining was used to observe the apoptosis of the cells in response to transfection with a small interfering RNA targeting GRP78 (pSHlSi-GRP78). Western blotting was employed to detect GRP78 expression in pSHlSi-GRP78-rransfected cells after exposure to 8 μmol/L cisplatin for 24, 48 and 72 h. Results Exposure of the cells to 8 μmol/L cisplatin for 24, 48 and 72 h resulted in a cell survival rate of 83.13%, 54.22% and 35.79%, respectively, but the cell apoptosis rate was only 10.8% at 24 h. Transfection of MDA-MB-231 cells with pSHlSi-GRP78 caused a cell apoptosis rate of 24.6%, which increased to 48.9% in cells with both pSHlSi-GRP78 transfection and cisplatin exposure. Cisplatin exposure caused an initial up-regulation followed then by a down-regulation of GRP78 expression in MDA-MB-231 cells, while pSHlSi-GRP78 transfection produced an obvious down-regulation of GRP78 expression. Conclusions Inhibition of GRP78 expression increases the apoptosis and enhance cisplatin chemosensitivity of breast cancer cells in vitro, suggesting the value of GRP78 as a potential therapeutic target in the clinical treatment of breast cancer.关键词
乳腺癌/葡萄糖调节蛋白78/小干扰RNA/顺铂/凋亡Key words
breast cancer/glucose-regulated protein 78/small interfering RNA/cisplatin/apoptosis引用本文复制引用
浦龙健,黄莹莹,李阳,徐锦程,蒋琛琛,刘浩,蒋志文..siRNA沉默葡萄糖调节蛋白78可增强乳腺癌细胞对顺铂的敏感性[J].南方医科大学学报,2013,33(1):44-47,4.基金项目
国家自然科学基金(81000992,81072207) （81000992,81072207）
安徽省教育厅自然科学研究重点项目(KJ2012A201) （KJ2012A201）
安徽省自然科学基金(1208085MH136) （1208085MH136）
