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

Inhibitory effects and mechanism of SAHA combined with Erlotinib on EGFR-TKI resistant lung cancer cell line H1975 cells

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(pAKT)、哺乳动物雷帕霉素靶蛋白(m TOR)、磷酸化哺乳动物雷帕霉素靶蛋白(p-m TOR)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/m TOR信号通路有较强的抑制作用。结论 SAHA联合厄洛替尼对EGFR-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/m TOR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 Erlotinib on EGFR-TKI resistant lung cancer cell line H1975 cells. Methods The inhibitory effects of SAHA,Erlotinib 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 PI3 K,AKT,p-AKT,m TOR and p-m TOR protein in cells. Results SAHA and Erlotinib showed growth inhibition effects on H1975 cells with a dose-dependent mannerand 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 PI3 K/AKT/m TOR 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 PI3 K/AKT/m TOR signaling pathway.