五味子乙素下调IGFBP2表达抑制吉非替尼耐药肺癌细胞增殖

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。

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

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.