胰岛素抗性对肝癌HepG2细胞生物学功能及顺铂敏感性的影响

摘要

[ ABSTRACT] AIM:To investigate the effect of insulin resistance ( IR) on the biological function of hepatocellu-lar carcinoma ( HCC) and sensitivity to cisplatin.METHODS:IR was induced in HepG2 cells via incubation with a high concentration of insulin.Afterwards, the effects of IR on adhesion, migration, invasion and sensitivity to cisplatin of the cells were detected.RESULTS:The results indicated that glucose consumption was reduced in the IR cells.The expres-sion of the insulin receptor and glucose transporter 2 was down-regulated.Furthermore, HepG2/IR cells displayed marked-ly enhanced adhesion, migration, and invasion.These cells exhibited a lower sensitivity to cisplatin.On the contrary, HepG2/IR cells exhibited decreased adhesion and invasion after treatment with the insulin sensitizer pioglitazone hydrochlo-ride.CONCLUSION:IR is closely related to drug resistance, adhesion, migration and invasion in HepG2 cells.These findings may help explain the clinical observation of the limited efficacy of chemotherapy on a background of IR.%目的：研究胰岛素抗性在原发性肝癌细胞中的生物学功能及对顺铂抗癌药物的抗药敏感性的影响。方法：利用高浓度的胰岛素连续培养HepG2细胞72 h获得抗胰岛素的HepG2细胞（ HepG2／IR），检测HepG2／IR细胞的黏附、迁移和侵袭的能力改变以及对顺铂的敏感性；同时利用流式细胞术测定HepG2和HepG2／IR中胰岛素受体和葡萄糖转运蛋白2的表达情况。结果：胰岛素抗性HepG2／IR细胞中葡萄糖消耗量显著降低；胰岛素受体和葡萄糖转运蛋白2表达下调；而HepG2／IR细胞的黏附、迁移和侵袭能力明显增强；同时HepG2／IR细胞对顺铂的敏感性降低；但用吡格列酮处理HepG2／IR细胞后其黏附、迁移和侵袭能力显著减弱。结论：胰岛素抗性与HepG2细胞的耐药性、细胞黏附、迁移和侵袭能力密切相关。这有助于解释具有胰岛素抗性的癌症患者对化疗失敏的临床现象。