上皮-间质转化对EGFR突变型非小细胞肺癌细胞株PC-9放射敏感性的影响

摘要

Objective To explore the influence of epithelial mesenchymal transition(EMT)in radiosensi-tivity of EGFR-mutant NSCLC cell with acquired resistance to EGFR-TKI. Methods In this study,EGFR-mutant human lung adenocarcinoma cell line PC-9 and Gefitinib acquired resistance cell line PC-9/AB were used. Western blot was used to assess EMT. Wound healing migration assay was tested. CCK8,colony formation and flow cytome-try were used to evaluate survival fraction ,as the sensitivity to irradiation. Results PC-9/AB displayed radioresis-tance(P<0.05). When EMT was reversed with CDH1,its radiosensitivity was significantly higher than PC-9/AB (P < 0.05). PC-9/TGF also displayed radioresistance (P < 0.05),as well as EMT phenotype presented. Conclusion EMT enhanced the radioresistance of EGFR-mutant NSCLC cell with acquired resistance to EGFR-TKI, possibly through TGF-βpathway.%目地:探讨上皮-间质转化(EMT)在EGFR突变型非小细胞肺癌(NSCLC)细胞EGFR-TKI获得性耐药前后放射敏感性变化中的作用.方法:选用EGFR19外显子缺失突变的人肺腺癌细胞PC-9及对吉非替尼获得性耐药的PC-9/AB.采用免疫印迹法检测EMT相关蛋白;划痕实验检测细胞迁移能力;CCK-8法、克隆形成实验以及流式细胞术检测细胞放射敏感性.结果:PC-9/AB出现EMT,其放射敏感性显著低于PC-9(P<0.05);逆转EMT的PC-9/AB-CDH1放射敏感性较PC-9/AB恢复(P<0.05);PC-9/TGF发生EMT的同时放射敏感性下降(P<0.05).结论:EMT是EGFR突变型NSCLC细胞EGFR-TKI耐药后发生放射抵抗的机制之一,该机制可能通过TGF-β通路实现.