CD146对获得性Erlotinib耐药肺腺癌细胞上皮-间充质转化的影响  

CD146 contributes to epithelial-mesenchymal transition of acquired resistance to erlotinib in non-small cell lung cancer in vitro and in vivo

作　　者：张晓菊[1] 汪铮[1] 安云霞[1] 张亚飞[1] 刘正国[2] 孔令非[2] 

机构地区：[1]河南省人民医院郑州大学人民医院呼吸内科,郑州450003 [2]河南省人民医院郑州大学人民医院病理科,郑州450003

出　　处：《中华实验外科杂志》2014年第8期1642-1644,共3页Chinese Journal of Experimental Surgery

摘　　要：目的 探讨CD146对获得性Erlotinib耐药肺腺癌细胞上皮-间充质转化（EMT）的作用及机制.方法 采用不同浓度的Erlotinib作用于肺腺癌细胞株H1650,诱导其产生耐药（H1650ER）;免疫荧光法及Western blot检测耐药前后上皮型钙黏蛋白（E-cadherin）、波形蛋白（Vimentin）、CD146的表达变化;小干扰RNA（siRNA）干扰H1650ER细胞中CD146的表达,利用Transwell侵袭小室及细胞计数试剂盒（CCK-8）实验分别评价肺腺癌细胞侵袭及增殖能力,Western blot 检测相关蛋白的表达变化.结果 获得性Erlotinib耐药肺腺癌细胞H1650ER中CD146及Vimentin 蛋白的表达量分别为0.474±0.013和0.465±0.012,显著高于耐药前（P＜0.05）;而E-cadherin蛋白的表达量为0.180±0.011,明显低于耐药前（P＜0.05）.CD146-siRNA干扰H1650ER细胞CD146的表达后可明显抑制其增殖能力,与对照组比较差异有统计学意义（P＜0.05）;CD146-siRNA干扰后细胞侵袭力亦下降（P＜0.05）.结论 获得性Erlotinib耐药肺腺癌产生EMT并CD146表达显著上调;抑制CD146的表达可下降其侵袭及增殖能力.Objective To elucidate the impact of CD146 on epithelial-mesenchymal transition （EMT） of acquired resistance to erlotinib in non-small cell lung cancer （NSCLC）,thus to reveal the molecular mechanism of CD146 involved in the EMT and in the metastasis of cancer cells.Methods NSCLC cell line H1650 was used to establish the subline resistant to erlotinib （H1650ER）.The expression of E-cadherin,Vimentin and CD146 in the resistant cells was examined using immunostaining and Western blotting.CD146 was silenced by RNA interference in H1650ER,and invasion assay was performed to characterize the resistant cells.The effects of CD146 on cell proliferation and invasion were analyzed.Results The quantity of CD146 expression and Vimentin expression in lung adenocarcinoma cancer cell H1650ER were 0.474 ± 0.013 and 0.465 ± 0.012,significantly higher than before resistance （P ＜ 0.05）.The E-cadherin protein expression was 0.180 ± 0.011,significantly lower than before resistance （P ＜ 0.05）.As compared with the control group,small interfering RNA （siRNA）-mediated down-regulation of CD146 suppressed the proliferation and invasion ability of H1650ER （P ＜ 0.05）.Conclnsion CD146 contributes to EMT of acquired resistance to erlotinib in NSCLC in vitro.It suggests that CD146 is a potential molecular target in the treatment of NSCLC.

关 键 词：肺腺癌 ERLOTINIB 上皮-间充质转化 小干扰RNA 

分 类 号：R734.2[医药卫生—肿瘤]