胰岛素抵抗的人肝癌细胞HepG2对多柔比星的敏感性  

The sensitivity of insulin-resistant hepatoma HepG2 cells to adriamycin

作　　者：孙静[1] 易娟 陈静[1] 程杰[1] 李林静[1] 魏虎来[1] 

机构地区：[1]兰州大学基础医学院医学实验中心,甘肃省新药临床前研究重点实验室,兰州730000

出　　处：《肿瘤》2009年第11期1036-1039,共4页Tumor

基　　金：甘肃省科技计划资助项目(编号:0803RJZA062)

摘　　要：目的:观察胰岛素抵抗(insulin resistance,IR)的人肝癌细胞对抗癌药物多柔比星(adriamycin,ADM)的敏感性,并探讨其抗药机制。方法:采用5×10-6moL/L胰岛素诱导(36和48h)人肝癌细胞HepG2建立HepG2/IR细胞模型,并用盐酸吡格列酮(pioglitazone hydrochloride,PH)逆转HepG2/IR细胞的IR状态。MTT法检测HepG2/IR细胞对ADM的敏感性,FCM检测P糖蛋白(P-glycoprotein,P-gp)的表达水平,实时荧光定量RT-PCR检测多药耐药基因1(multiple drug resistance 1,MDR1)mRNA的表达。结果:HepG2/IR细胞对ADM的敏感性降低(P<0.05),MDR1 mRNA的表达量分别是HepG2细胞的1.62倍(胰岛素诱导36h)和5.21倍(胰岛素诱导48h),P-gp蛋白的阳性表达率分别提高了47.50%(胰岛素诱导36h)和189.05%(胰岛素诱导48h)。PH可逆转HepG2/IR细胞MDR1/P-gp的表达增加以及逆转细胞对ADM的抗药性。结论:胰岛素诱导的人肝癌细胞HepG2/IR可通过增加MDR1/P-gp的表达,使细胞对抗癌药物产生抗药性。Objective：To investigate the sensitivity of human hepatoma insulin-resistant HepG2 （HepG2/IR） cells to chemo- therapeutic drug adriamycin, and to explore the drug-resistant mechanism of HepG2/IR cells. Methods ： Insulin-resistant HepG2 cells （HepG2/IR） were established by incubating human hepatoma cells with 5× 10 -6 moL/L of insulin for 36 and 48 h. The insulin sensiti- zer pioglitazone was used to reverse insulin resistance of HepG2/IR cells. The cellular sensitivity was detected with MTT assay, P-glycoprotein （P-gp） expression was measured with flow cytometry （ FCM）, and the expression of multiple drug resistance 1 （ MDR1 ） mRNA was assessed by real-time fluorescence quantitative RT-PCR. Results：The sensitivity of HepG2/IR ceils to adriamycin decreased （P 〈 0.05 ）, while the expression of MDR1 gene was up-regulated significantly （ 1.62 folds at 36 h and 5.21 folds at 48 h）, and positive ex- pression rate of P-gp was increased by 47.50% at 36 h and 189.05% at 48 h. The resistance to adrimycin and the enhancement of MDR1/P-gp expression in HepG2/IR cells could be reversed by insulin sensitizer pioglitazone. Conclusion： The insulin induces resis- tance of hepatocarcinoma cells （HepG2/IR） to chemotherapeutic agents by enhancing the expression of MDR1/P-gp.

关 键 词：肝肿瘤 胰岛素抗药性 P糖蛋白类 抗药性 细胞 HEPG2 多柔比星 吡格列酮 

分 类 号：R735.7[医药卫生—肿瘤]