SAHA联合厄洛替尼对EGFR-TKI耐药肺癌细胞株H1975的生长抑制作用及机制

摘要

目的 探讨SAHA单独及联合厄洛替尼对表皮生长因子酪氨酸激酶抑制剂(EGFR-TKI)耐药细肺癌胞株H1975的生长抑制及可能的机制研究.方法 通过CCK-8、平板克隆及Transwell小室侵袭实验评判SAHA、厄洛替尼单药及联合作用于H1975细胞后对细胞的抑制作用,Western blot法分析用药后细胞内磷脂酰肌醇3-激酶(PI3K)、丝氨酸/苏氨酸蛋白激酶( AKT)、磷酸化丝氨酸/苏氨酸蛋白激酶( p-AKT)、哺乳动物雷帕霉素靶蛋白( mTOR)、磷酸化哺乳动物雷帕霉素靶蛋白(p-mTOR)蛋白的表达量.结果 SAHA、厄洛替尼对H1975 细胞的生长抑制呈浓度依赖型,两药联合具有协同效果.联合用药对肿瘤细胞的克隆形成及侵袭抑制作用明显强于单药;且联合用药对PI3K/AKT/mTOR信号通路有较强的抑制作用.结论 SAHA联合厄洛替尼对EG-FR-TKI耐药肺癌细胞株H1975的生长、克隆、侵袭具有协同抑制作用,可能与对PI3K/AKT/mTOR信号通路的抑制作用有关.%Objective To investigate the inhibition and possible mechanism of SAHA alone and combined with Er-lotinib on EGFR-TKI resistant lung cancer cell line H1975 cells. Methods The inhibitory effects of SAHA, Erlo-tinib and combined effect on cells were evaluated by CCK-8, colony formation assay and Transwell invasion assay. Western blot analysis was used to analyze the expression of PI3K, AKT, p-AKT, mTOR and p-mTOR protein in cells. Results SAHA and Erlotinib showed growth inhibition effects on H1975 cells with a dose-dependent man-nerand displayed synergistic inhibition effect. The combination of the drugs was significantly stronger than the single drug in the formation and invasion inhibition of tumor cells. The combined group had a strong inhibitory effect on the PI3K/AKT/mTOR signaling pathway. Conclusion SAHA combined with Erlotinib has synergistic inhibitory effects on the growth, cloning and invasion of EGFR-TKI lung cancer cell line H1975, which may be associated with inhibitory effects on the PI3K/AKT/mTOR signaling pathway.