反义寡脱氧核苷酸抑制多药耐药基因mdr1表达并逆转耐药肝癌细胞的体外试验研究  

Reversal of Drug-resistance Hepatoma Carcinoma Cells by Inhibition of Multidrug Resistance Gene mdr1 Expression with Antisense Oligodeoxyribonucleotide

作　　者：彭志平[1] 蒋明东[1] 尹晓玲[1] 文明[1] 李少林[1] 

机构地区：[1]重庆医科大学基础医学院,重庆市400016

出　　处：《中国药房》2011年第33期3108-3110,共3页China Pharmacy

摘　　要：目的:探讨反义寡脱氧核苷酸(ASODN)抑制多药耐药基因(mdr1)对耐阿霉素(ADM)肝癌细胞HepG2/ADM化疗敏感性的影响。方法:以多药耐药基因mdr1人工合成寡脱氧核苷酸(ODN),其中ODN分为ASODN和正义寡脱氧核苷酸(SODN),并采用脂质体转染技术将ODN与HepG2/ADM共培养,试验分为反义寡脱氧核苷酸(mdr1-ASODN)处理组、正义寡脱氧核苷酸(mdr1-SODN)对照组和空白对照组,通过逆转录聚合酶链式反应和蛋白免疫印迹法观察HepG2/ADM细胞中mdr1mRNA及其蛋白表达情况;MTT法观察HepG2/ADM细胞转染mdr1-ASODN前、后对化疗药物(ADM、顺铂、5-氟尿嘧啶)的敏感性。结果:与mdr1-SODN对照组和空白对照组比较,mdr1-ASODN处理组HepG2/AMD细胞中mdr1mRNA及其蛋白表达均明显降低(P<0.05);与转染前比较,HepG2/ADM细胞的增殖抑制率明显增加(P<0.05)。结论:ASODN能有效抑制mdr1基因表达,并恢复肝癌HepG2/ADM细胞对化疗药物的敏感性。OBJECTIVE： To investigate the effects on chemosensitivity of adriamycin （ADM）-resistant hepatoma carcinoma cells （HepG2/ADM） by inhibition of multidrug resistance 1 （mdr1） expression with antisense oligodeoxyribonucleotide （ASODN）. METHODS： Oligodeoxyribonucleotide （ODN） of mdrl gene was synthesized and included ASODN and SODN, then transfected into HepG2/ADM hepatoma carcinoma cells by liposome transfection reagent. HepG2/ADM hepatoma carcinoma cells were divided into mdr1-ASODN treatment group, mdr1-SODN control group and blank control group. RT-PCR and Western blotting were used to detect their mRNA and protein expressions of mdr1. The sensitivity of HepG2/ADM cells before and after transfected by mdr1-ASODN to chemotherapeutic drugs （ADM, cisplatin, 5-fluorouracil） was evaluated by MTT assay. RESULTS： Compared with mdr1-SODN control group and blank control group, the mRNA and protein expressions of mdr1 were significantly decreased in mdr1-ASODN treatment group （P〈 0.05）; compared with before transfection, the inhibitory effects of chemotherapeutic agents on the proliferation of Hep（32/ADM hepatoma carcinoma cells were increased in vitro （P〈0.05）. CONCLUSION： ASODN inhibits the expressions of mdr, and enhances the sensitivity of HepG2/ADM cells to chemotherapeutic agents in vitro.

关 键 词：反义寡脱氧核苷酸 肝癌细胞 药敏试验 多药耐药 表达 

分 类 号：R735.7[医药卫生—肿瘤]