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)诱导激活EGFR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，我们报道了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Survivin表达的影响。免疫印迹分析显示，在EGFR突变阳性的非小细胞肺癌细胞中，吉非替尼可能通过抑制PI3K-AKT信号通路下调Survivin的表达。稳定过表达Survivin可减弱吉非替尼诱导的细胞凋亡，并抑制吉非替尼的抗肿瘤作用。我们的结果表明，Survivin的下调在吉非替尼诱导EGFR突变阳性的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.