癌变·畸变·突变2017，Vol.29Issue(3)：199-204,6.DOI:10.3969/j.issn.1004-616x.2017.03.008
磁性纳米颗粒载ABCG2-siRNA逆转乳腺癌细胞对阿霉素耐药性的研究
ABCG2-siRNA loaded magnetic nanoparticles enhanced therapeutic effect of adriamycin on multidrug resistant breast cancer cells
摘要
Abstract
OBJECTIVE: To investigate the use of siRNA to silence the breast cancer resistance protein (BCRP/ABCG2) on overcoming multidrug resistance in breast cancer cells. METHODS:The morphologic,particle size,surface potential of magnetic nanoparticles (polyMAG) were characterized by transmission electron microscopy and by zeta potential analyzer,and the binding capacity of siRNA and polyMAG were investigated by gel retardation assay. We used polyMAG as a carrier to deliver several concentrations of siRNA (5,10,20,50,100 nmol/L) effectively into MCF-7/ADR cells. Quantitative real-time PCR (qPCR) and Western blotting were used to detect ABCG2 levels. CCK-8 and Calcein-AM/PI were stained and used to detect cell proliferation. RESULTS:The average size and zeta potentials of polyMAG was about 100 nm and 29.6 mv. Gel retardation assay confirmed that siRNA was well packaged into polyMAG under polyMAG/siRNA ratios 1:1 and 1:2. Cell viability of MCF-7/ADR was reduced while siRNA concentrations changed from 20 nmmol/L to 100 nmmol/L,compared with non-siRNA transfection (P<0.05). Expression of ABCG2 mRNA was significantly down-regulated in the 20 nmol/L polyMAG-siRNA transfected group,which was about 1/8 of the un-transfected group (P<0.05),and apoptotic cells were significantly increased compared with other groups. 50 nmol/L polyMAG-siRNA significantly interfered with the expression of ABCG2 protein (P<0.05). CONCLUSION:polyMAG-siRNA effectively perturbed the ABCG2 expression and enhanced DOX susceptibility of MCF-7/ADR to overcome multidrug resistance in breast cancer cells.关键词
磁性纳米粒子/siRNA/乳腺癌耐药蛋白/多药耐药Key words
magnetic nanoparticles/siRNA/breast cancer resistance protein/multidrug resistance分类
医药卫生引用本文复制引用
朱婷,万丽丽,刘丽桃,阮海英,饶茜,谢妮..磁性纳米颗粒载ABCG2-siRNA逆转乳腺癌细胞对阿霉素耐药性的研究[J].癌变·畸变·突变,2017,29(3):199-204,6.基金项目
广东省自然科学基金(2016A030313029) （2016A030313029）
广东省科技计划项目(2014A020212038) （2014A020212038）
深圳市科技创新委基础研究项目(JCYJ20150330102720122) （JCYJ20150330102720122）
深圳市科技创新委国际合作项目(GJHZ20160301163138685) （GJHZ20160301163138685）
