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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

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【作者】 孙静易娟陈静程杰李林静魏虎来

【Author】 SUN Jing,YI Juan,CHEN Jing,CHENG Jie,LI Lin-jing,WEI Hu-lai (Laboratory Center for Medical Sciences,School of Basic Medicine,Lanzhou University,Key Laboratory of Preclinical Study for New Drugs of Gansu Province,Lanzhou 730000,China)

【机构】 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

【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。

【Abstract】 Objective:To investigate the sensitivity of human hepatoma insulin-resistant HepG2 (HepG2/IR) cells to chemotherapeutic 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 sensitizer 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 cells 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 expression 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.

【基金】 甘肃省科技计划资助项目(编号:0803RJZA062)
  • 【分类号】R735.7
  • 【被引频次】5
  • 【下载频次】186
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