五味子乙素下调IGFBP2表达抑制吉非替尼耐药肺癌细胞增殖

The role of Schisandrin B in inhibiting proliferation of gefitinib-resistant lung cancer cells via down-regulation of IGFBP2 expression

目的:探讨五味子乙素(Sch B)抑制吉非替尼(Gef)耐药肺癌细胞的增殖作用及机制。方法:采用浓度梯度法驯化PC9细胞,获得PC9/GR耐药细胞,比较PC9与PC9/GR细胞增殖、胰岛素样生长因子结合蛋白2(IGFBP2)表达情况;经Sch B处理后,观察PC9/GR细胞增殖、凋亡及IGFBP2和磷酸化p-AKT、p-mTORC1表达情况,并利用IGFBP2过表达腺病毒转染技术验证IGFBP2在Sch B抑制PC9/GR细胞增殖中的作用。结果:PC9/GR细胞内IGFBP2表达高于PC9细胞(P<0.05),Sch B处理后,PC9/GR细胞存活率下降,细胞凋亡增加,IGFBP2表达和AKT、mTORC1磷酸化下降(P<0.05)。IGFBP2-OE转染后PC9/GR细胞内p-AKT、p-mTORC1明显增加(P<0.05),Sch B对PC9/GR增殖抑制作用下降(P<0.05)。结论:Sch B下调IGFBP2表达,抑制PC9/GR细胞增殖。

Objective:To investigate the role of Schisandrin B(Sch B)in inhibiting proliferation of gefitinib(Gef)resistant lung cancer cells and its molecular mechanism.Methods:PC9/GR(Gefitinib resistant PC9 cells)resistant cells were domesticated with gradient concentration of Gef and maintained with 200 mmol/L Gef.The difference of IGFBP2 expression and the viability between PC9 and PC9/GR cells were analyzed.The viability,apoptosis,IGFBP2 expression and phosphorylation of AKT and mTORC1were measured with and without Sch B treatment.Lentivirus transfection to obtain IGFBP2 overexpression(OE)cells was applied to confirm the role of IGFBP2 on proliferation inhibition of Sch B in PC9/GR cells.Results:The expression of IGFBP2 in PC9/GR cells was higher than that in PC9 cells(P<0.05).After Sch B treatment,the survival rate,IGFBP2 expression and phosphorylation of AKT and mTORC1 decreased(P<0.05),whereas the apoptosis increased(P<0.05).The overexpression of IGFBP2 increased the phosphorylation of AKT and mTORC1 but alleviated the proliferation inhibition of Sch B in PC9/GR cells(P<0.05).Conclusion:Sch B induces proliferation inhibition via down-regulating expression of IGFBP2 in PC9/GR cells.