目的:探讨肿瘤干细胞在非小细胞肺癌(NSCLC)细胞上皮间质转化(EMT)介导的EGFR-TKIs获得性耐药中的作用。方法:选用EGFR基因19号外显子突变型人NSCLC细胞株PC-9;经吉非替尼诱导成获得性耐药细胞株PC-9/AB。免疫印记检测EMT相关蛋白;CCK8法检测细胞对吉非替尼敏感性;流式细胞术检测细胞株CSC比例。结果:PC-9/AB出现EMT,PC-9/AB较PC-9对吉非替尼敏感性显著下降(P〈0.01);PC-9/AB的CSC比例较PC-9显著增加(P〈0.05)。结论:EMT是NSCLC EGFR-TKIs获得性耐药的机制之一,该机制与CSC生成增加有关。
Objective To explore the role of cancer stem cells in EMT-induced acquired resistance to EGFR-TKIs in NSCLC.Methods The EGFR del E746-A750 mutated human lung adenocarcinoma PC-9 cell line and gefitinib acquired resistance cell line PC-9 / AB were used in this study.EMT was assessed by western blotting assay.The sensitivity to gefitinib was tested with CCK8.Flow cytometry for antibody analysis was used to quantify CSCs within the cell lines.Results Compared with PC-9,PC-9 / AB underwent EMT and showed notable resistance to gefitinib(P〈0.01).Compared with PC-9,the proportions of CSCs were much higher in PC-9 / AB.Conclusion EMT plays an important role in the acquired resistance to EGFR-TKIs in NSCLC,possibly through the up-regulation of CSCs.