IGF-ⅠR信号通路在西妥昔单抗抗HepG2细胞增殖中的作用

Role of IGF-ⅠR signaling pathway in the anti-proliferation of cetuximab to HepG2 cells

目的探讨IGF-ⅠR信号通路在西妥昔单抗抗HepG2细胞增殖中的作用。方法选用浓度递增的西妥昔单抗(5～500)mg/mL、胰岛素样生长因子(IGF)(2.5～250)μmol/L及其抑制剂aIR3(2.5～250)μmol/L,单独或联合作用于HepG2细胞,观察IGF与aIR3对西妥昔单抗抗HepG2增殖的影响。结果细胞培养72 h后,单药西妥昔单抗对HepG2细胞增殖的抑制作用呈浓度依赖性,西妥昔单抗联合aIR3组增殖抑制率在相应浓度下均显著高于同浓度的西妥昔单抗组(均为P<0.01),IGF(10～250)μmol/L与西妥昔单抗(20～500)mg/mL联合组增殖抑制率均显著低于相应浓度的西妥昔单抗组(均为P<0.01)。结论 IGF-ⅠR通路可影响西妥昔单抗抗HepG2细胞增殖的作用,可能是肝癌细胞株对西妥昔单抗耐药的机制之一。

Objective To investigate the role of IGF- I R signaling pathway in the anti-proliferation of cetuximab to HepG2 cells. Methods Increasing concentrations of cetuximab （5-500） mg/mL, insulin-like growth factor （IGF） （2.5-250） μmol/L and its inhibitor aiR3 （2.5-250）μmol/L, alone or in combination were administrated to HepG2 cells. The inhibitory effects of the drugs on cell proliferation were observed. Results After 72 h cell culture, the single agent of cetuximab inhib- ited the proliferation of HepG2 cells in a dose-dependent manner. The growth inhibition rates of cetuximab combined aiR3 group at the corresponding concentrations were significantly higher than that of cetuximab group （all P 〈 0.01）. However, the proliferation inhibition rates of IGF （10-250） μmol/L combined cetuximab （20-500） mg/mL were significantly lower than that of cetuximab group （all P 〈 0.01）. Conclusion IGF- l R pathway can affect the anti-proliferation of cetuximab to HepG2 cells, which may be one of the mechanisms of hepatocellular carcinoma cell lines resistance to cetuximab.