胰岛素抵抗肝癌细胞IGF-1R/NF-κB表达及多药耐药机制研究

doi:10.3969/j.issn.1672-5069.2016.06.016

实用肝脏病杂志 ›› 2016, Vol. 19 ›› Issue (6): 704-708.doi: 10.3969/j.issn.1672-5069.2016.06.016

胰岛素抵抗肝癌细胞IGF-1R/NF-κB表达及多药耐药机制研究

王以浪，印滇，杨莉，张亮，姚登福

226001 江苏省南通市第一人民医院肿瘤科（王以浪，印滇，杨莉，张亮）；南通大学附属医院临床研究中心（姚登福）

收稿日期:2016-06-20 出版日期:2016-11-10 发布日期:2016-11-28
通讯作者: 姚登福，E-mail：yaodf@ahnmc.com
作者简介:王以浪，男，34 岁，医学硕士，主治医师。从事肿瘤学基础及临床研究。E-mail：oncowang@163.com
基金资助:
南通市卫生局青年医学人才科研基金项目（编号：WQ2014005）

Expression of IGF-1R/NF-kappa B and multi-drug resistance in insulin resistance-HepG2 and HepG2.2.15 cells in vitro

Wang Yilang，Yin Dian，Yang Li，et al.

Department of Oncology，Research Center of Clinical Medicine，First People’s Hospital Affiliated to Nantong University，Nantong，226001，Jiangsu Province，China

Received:2016-06-20 Online:2016-11-10 Published:2016-11-28
Contact: Yao Dengfu，E-mail:yaodf @ahnmc.com

摘要/Abstract

摘要： 目的探讨胰岛素抵抗（IR）肝癌细胞胰岛素样生长因子1受体（IGF-1R）和核因子-κB（NF-κB）表达变化及多药耐药（MDR）发生机制。方法采用高浓度胰岛素诱导人肝癌细胞（HepG2和HepG2.2.15）建立胰岛素抵抗（IR）细胞模型。采用Western blot 法检测胰岛素受体（InsR）、IGF-1R、NF-κB 和 P-糖蛋白（P-gp）表达变化。使用流式细胞仪（Annexin V-FITC法）检测阿霉素对细胞凋亡的影响。结果分别用100 nmol/L 和 1 000 nmol/L 胰岛素培养 HepG2 和 HepG2.2.15 细胞 48 h，成功建立 IR 肝癌细胞模型；IR 肝癌细胞 IGF-1R、NF-κB、P-gp 表达上调，而InsR 表达下调；应用 25μg/mL 阿霉素作用细胞 24 h 后，IR-HepG2 细胞组凋亡率（31.1%±1.9%）显著低于HepG2 细胞组【（49.7%±2.2%），P＜0.01】，IR-HepG2.2.15细胞凋亡率【（20.1±1.7） %】显著低于 HepG2.2.15 细胞【（33.8±1.8）%，P＜0.01】；HepG2.2.15 和 IR-HepG2.2.15 细胞凋亡率分别较 HepG2 和 IR-HepG2 细胞显著降低（P＜0.01）。结论 IGF-1R/NF-κB/P-gp 过表达可能介导 IR 肝癌细胞对阿霉素的多药耐药。

关键词: HepG2细胞, 胰岛素抵抗, 胰岛素样生长因子1受体, 核因子-κB, P 糖蛋白, 多药耐药

Abstract: Objective To investigate the expression of insulin-like growth factor 1 receptor（IGF-1R），nuclear factor-κB（NF-κB） and the mechanism of multi-drug resistance（MDR） in insulin resistance（IR）- hepatoma cells in vitro. Methods The human hepatoma cells（HepG2 and HepG2.2.15） were induced by high concentration of insulin to establish a insulin resistance model. The expression of insulin receptor （InsR），IGF-1R，NF kappa B，P glycoprotein（P-gp） were detected by Western bloting and the effect of adriamycin on cell apoptosis were detected by flow cytometry（annexin V-FITC）. Results IR model of hepatoma cells were established successfully by subjecting the HepG2 and HepG2.2.15 cells to 100 nmol/L and 1 000 n mol/L insulin respectively for 48 hours. The expression of IGF-1R，NF-kappa B and P-gp were up-regulated in IR hepatoma cells，while the InsR expression was down-regulated；After treatment of the two cells with 25 μg/ml doxorubicin for 24 hours，the apoptosis rate of IR-HpeG 2 cells （31.1% ±1.9%） was significantly lower than HepG2 cells [（49.7±2.2）%，P＜0.01]，and the apoptosis rate of IR-HepG2.2.15 cells（20.1±1.7）% was significantly lower than HepG2.2.15 cells[（33.8±1.8）%，P＜0.01]；The apoptotic rates of HepG2.2.15 or IR-HepG2.2.15 cells were significantly lower than HepG2 or IR-HepG2 cells（P＜0.01），respectively. Conclusion The expression of IGF-1R， NF-kappa B and P-gp are up-regulated in IR-hepatoma cells，which might induce the MDR to adriamycin.

Key words: HepG2 cells, Insulin resistance, Insulin-like growth factor I receptor, NF-kappa B, P-glycoprotein, Multi-drug resistance

王以浪，印滇，杨莉，张亮，姚登福. 胰岛素抵抗肝癌细胞IGF-1R/NF-κB表达及多药耐药机制研究[J]. 实用肝脏病杂志, 2016, 19(6): 704-708.

Wang Yilang，Yin Dian，Yang Li，et al.. Expression of IGF-1R/NF-kappa B and multi-drug resistance in insulin resistance-HepG2 and HepG2.2.15 cells in vitro[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2016, 19(6): 704-708.

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胰岛素抵抗肝癌细胞IGF-1R/NF-κB表达及多药耐药机制研究

Expression of IGF-1R/NF-kappa B and multi-drug resistance in insulin resistance-HepG2 and HepG2.2.15 cells in vitro

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