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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 investigate the effects of Afatinib, an inhibitor of Pan-HER, and PF-04691502 (PF), a phosphoinositide 3-kinase inhibitor of PI3K, on the proliferation of epidermal growth factor receptor in vitro antitumor effect of epidermal growth factor receptor (EGFR) inhibitor-resistant non-small cell lung cancer (NSCLC) cell line H1975. Methods The effects of Afatinib and PF alone on the proliferation and migration of drug-resistant non-small cell lung cancer cell line H1975 were analyzed by MTS assay, cell scratch healing assay and flow cytometry. Results Afatinib and PF alone significantly inhibited the proliferation of H1975 cells, and the inhibitory effect was enhanced with the increase of concentration. When Afatinib and PF were combined, the proliferation and migration of H1975 cells were significantly inhibited. Afatinib and PF alone combined with PF (P <0.05). The apoptosis rates of Afatinib and PF were significantly higher than those of control group (P <0.05). Conclusion Pan-HER irreversible inhibitor Afatinib and PI3Kα inhibitor PF-04691502 (PF) alone have strong inhibitory effect on drug-resistant non-small cell lung cancer cell line H1975, and when combined with Afatinib and PF, Strain H1975 has a synergistic inhibitory effect.