阿法替尼与PF-04691502单用及联合对H1975细胞体外抗肿瘤作用研究

Anti-tumor effect of afatinib and PF-04691502 separately or combined on NSCLC H1975 cells in vitro

目的研究Pan-HER不可逆抑制剂阿法替尼(Afatinib)和磷脂酰基醇3-激酶(phosphoinositide 3-kinase,PI3K)α抑制剂PF-04691502(PF)单用及联合对表皮生长因子受体(epidermal growth factor receptor,EGFR)抑制剂耐药的非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞株H1975的体外抗肿瘤作用。方法通过MTS法、细胞划痕愈合实验、流式细胞术检测细胞周期和凋亡分析Afatinib和PF单药及联合对耐药性非小细胞肺癌细胞株H1975增殖、迁移等的影响。结果 Afatinib和PF单用对H1975细胞增殖有明显抑制作用,且抑制作用随浓度增加而加强;Afatinib和PF联合时对H1975细胞增殖、迁移均有明显协同抑制作用;Afatinib和PF单药和联合作用均主要使细胞阻滞在G1期(P<0.05);Afatinib和PF单用时较对照组的细胞凋亡率增加,且当两者联合作用时凋亡率增加更显著(P<0.05)。结论 Pan-HER不可逆抑制剂Afatinib和PI3Kα抑制剂PF-04691502(PF)单用对耐药性非小细胞肺癌细胞株H1975有较强抑制作用,且当Afatinib和PF联合时对非小细胞肺癌细胞株H1975有协同抑制作用。

Objective To study the anti-tumor effect of separated or combined application of Pan-HER irreversible inhibitor afatinib and phosphoinositide 3-kinase α （PI3Kα） inhibitor PF-04691502 on epidermal growth factor receptor （EGFR） inhibitor-resistant non-small cell lung cancer （NSCLC） H1975 cells in vitro. Methods Effects of afatinib and PF-04691502 （PF） separated or combined application on the proliferation and migration of H1975 cells were analyzed by cell cycle and apoptosis with MTS assay, wound-healing assay, and flow cytometry. Results Afatinib and PF alone significantly inhibited the proliferation of H1975 cells in a dose-dependent manner. Afatinib combined with PF showed an evident synergetic inhibitory effect. Afatinib and PF separated or combined application both induced cell cycle arrest at G1 phase （P〈0.05）. As compared to the control group, afatinib and PF alone promoted cell apoptosis, and their combination induced a higher apoptotic rate of H1975 cells （P〈0.05）. Conclusion Pan-HER irreversible inhibitor afatinib and PI3Kα inhibitor PF alone shows significant antitumor effects on drug-resistant NSCLC H1975 cells. Moreover, their combination exhibits synergistic anti-tumor effects.