小分子干扰RNA对非小细胞肺癌MRP基因和药物敏感性的影响  

Effects of siRNA on multidrug resistance associated protein gene and chemotherapy drug sensitivity in non-small cell lung cancer

作　　者：徐萌[1] 朱新海[1] 盛良翮[1] 

机构地区：[1]暨南大学附属第一医院肿瘤科,广州510630

出　　处：《临床肿瘤学杂志》2008年第2期105-108,共4页Chinese Clinical Oncology

基　　金：国家自然科学基金项目(30772844);广东省自然科学基金项目(5006066);广东省医学科研基金项目(A2005360)

摘　　要：目的:观察小分子干扰RNA(siRNA)对非小细胞肺癌(NSCLC)MRP基因、药物敏感性和细胞凋亡的影响,探讨体外肺癌耐药的高效和特异逆转耐药策略。方法:采用MRP siRNA转染,RT-PCR检测多药耐药相关蛋白MRP mRNA表达水平,流式细胞仪检测MRP蛋白表达,MTT法检测MRP siRNA的细胞毒作用,碘化丙啶(PI)染色检测MRP siRNA的细胞凋亡作用。结果:SW1573/2R120细胞转染MRP siRNA后,MRP mRNA表达明显降低,转染24h、48h和72h后MRP siRNA组的MRP蛋白表达阳性率较对照组明显减低,MRP siRNA与对照组相比对细胞生长抑制并无统计学差异,未见明显影响细胞增殖;MRP siRNA明显增加10μM阿霉素对SW1573/2R120细胞生长的抑制,并随作用时间的延长而增强,MRP siRNA+ADM组细胞生长抑制作用与对照组相比有统计学差异,MRP siRNA协同阿霉素增强对化疗耐药肺癌细胞的凋亡作用。结论:MRPsiRNA可以明显逆转体外NSCLC MRP基因编码MRP蛋白的多药耐药。Objective：To investigate the effects of siRNA on MRP gene, drug sensitivity and apoptosis in non-small cell lung cancer, which achieved high-efficient and specific reversal of drug-resistance strategy in vivo. Methods：To use MRP siRNA transfection method, detected expression level of MRP mRNA through RT-PCR,used flow cytometry for MRP protein expression, MTT for cytotoxic effect of MRP siRNA and PI staining to determine apoptotic effect of MRP siRNA. Results：After MRP siRNA transfected to SW 1573/2R120 cells, expression of MRP mRNA obviously decreased. Trough 24h, 48h and 72h after transfection, positive rate of MRP protein expression in MRP siRNA group was obviously decreased compared with the control group. There was no statistical difference in MRP siRNA group compared with control group in inhibition of cell growth, no obvious influence on cell reproduction. MRP siRNA group obviously increased the inhibition of doxorubicin （ADM） on SW 1573/2R120cell growth, which increased with time. There was statistical difference in MRP siRNA ＋ ADM group in cell growth inhibition, compared with control group and MRP siRNA group. MRP siRNA with ADM enhanced apoptotic effect on drug-resisted lung cancer cell. Conclusion：MRP siRNA could reverse multidrug resistance of MRP protein coded by MRP gene in lung cancer in vivo.

关 键 词：小细胞肺癌 多药耐药 多药耐药相关蛋白 小分子干扰RNA 

分 类 号：R734.2[医药卫生—肿瘤]