Role of survivin in EGFR inhibitor-induced apoptosis in non-small cell lung cancers positive for EGFR mutations.

表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）诱导EGFR激活突变阳性的非小细胞肺癌（NSCLC）细胞凋亡的分子机制尚不清楚。在这项研究中，我们报告了EGFR-TKI吉非替尼对EGFR突变阳性NSCLC细胞中具有功能后果的抗凋亡蛋白生存素表达的影响。免疫印迹分析显示，吉非替尼下调EGFR突变阳性的NSCLC细胞中生存素的表达，可能是通过抑制PI 3 K-AKT信号通路。稳定过表达的生存素减弱吉非替尼诱导的细胞凋亡，也抑制了吉非替尼在人类肿瘤异种移植物中的抗肿瘤作用。我们的研究结果表明，下调生存素在吉非替尼诱导EGFR突变阳性NSCLC细胞凋亡中起着关键作用。

The molecular mechanism by which epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) induce apoptosis in non-small cell-lung cancer (NSCLC) cells that are positive for activating mutations of the EGFR remains unclear. In this study, we report the effects of the EGFR-TKI gefitinib on expression of the antiapoptotic protein survivin that have functional consequences in EGFR mutation-positive NSCLC cells. Immunoblot analysis revealed that gefitinib downregulated survivin expression, likely through inhibition of the PI3K-AKT signaling pathway, in NSCLC cells positive for EGFR mutation. Stable overexpression of survivin attenuated gefitinib-induced apoptosis and also inhibited the antitumor effect of gefitinib in human tumor xenografts. Our results indicate that downregulation of survivin plays a pivotal role in gefitinib-induced apoptosis in EGFR mutation-positive NSCLC cells.