论文部分内容阅读
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(Hep G2和Hep G2.2.15)建立胰岛素抵抗(IR)细胞模型。采用Western blot法检测胰岛素受体(Ins R)、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 000nmol/L胰岛素培养Hep G2和Hep G2.2.15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Ins R表达下调;应用25μg/m L阿霉素作用细胞24 h后,IR-Hep G2细胞组凋亡率(31.1%±1.9%)显著低于Hep G2细胞组【(49.7%±2.2%),P<0.01】,IR-Hep G2.2.15细胞凋亡率【(20.1±1.7)%】显著低于Hep G2.2.15细胞【(33.8±1.8)%,P<0.01】;Hep G2.2.15和IR-Hep G2.2.15细胞凋亡率分别较Hep G2和IR-Hep G2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。
Objective To investigate the changes of insulin-like growth factor 1 receptor (IGF-1R) and nuclear factor-κB (NF-κB) expression and the mechanism of multidrug resistance (MDR) in insulin resistance (IR) Methods Human hepatoma cells (Hep G2 and Hep G2.2.15) were induced by high concentration of insulin to establish insulin resistance (IR) cell model. Western blot was used to detect the expression of insulin receptor (Ins R), IGF-1R, NF-κB and P-glycoprotein (P-gp). The effect of doxorubicin on apoptosis was detected by flow cytometry (Annexin V-FITC). Results Hep G2 and Hep G2.2.15 cells were cultured with 100 nmol / L and 1 000 nmol / L insulin for 48 h, respectively. IR liver cancer cell model was established successfully. The expression of IGF-1R, NF-κB and P-gp were up-regulated (P <0.05). The apoptosis rate of IR-Hep G2 cells (31.1% ± 1.9%) was significantly lower than that of Hep G2 cells (49.7% ± 2.2%) after 24 h treatment with 25 μg / , P <0.01]. The apoptosis rate of IR-Hep G2.2.15 cells was significantly lower than that of Hep G2.2.15 cells [(33.8 ± 1.8)%, P <0.01], Hep G2.2.15 and The apoptosis rate of IR-Hep G2.2.15 cells was significantly lower than that of Hep G2 and IR-Hep G2 cells (P <0.01). Conclusion Overexpression of IGF-1R / NF-κB / P-gp may mediate multidrug resistance to doxorubicin in IR hepatoma cells.