广东医学Issue(10)：1473-1477,5.
IGF-1R信号通路及上皮-间质转化对非小细胞肺癌A549细胞EGFR-TKIs获得性耐药的作用
Roles of IGF-1R signal pathway and epithelial -mesenchymal transition in acquired resistance of EGFR -TKIs in non-small lung cancer A549 cells
摘要
Abstract
Objective To investigate the roles of insulin -like growth factor Ⅰreceptor ( IGF-1R) signal path-way and epithelial-mesenchymal transition ( EMT) in the acquired resistance of epidermal growth factor receptor -tyro-sine kinase inhibitors (EGFR-TKIs) in EGFR wild-type and K-ras mutant non -small cell lung cancer (NSCLC) A549 cells.Methods The EGFR wild-type and K-ras mutant human NSCLC A549 cells were used in this study.The gefitinib-resistant A549 cells (named as A549/GR cells) were created by repeated exposure to gefitinib .MTT assay was used to measure the cell proliferation .Wound-healing array and transwell array were used to determine the invasive and migratory capabilities of cells .The gene and protein expressions of E -cadherin, vimentin, IGF-1R, AKT, ERK and EGFR were determined by qRT -PCR and Western blot, respectively.Results The A549/GR cells acquired resistance to EGFR-TKIs, with significantly reduction in sensitivity to gefitinib (P<0.05).Compared with A549 cells, A549/GR cells presented with mesenchymal phenotype , accompanied by significant enhancement of invasion and migration ( P<0.05).The expression of mesenchymal cell marker vimentin was also significantly increased in A 549/GR cells ( P<0.05), with significant reduction in expression of epithelial cell marker E -Cadherin (P<0.05).No significant differ-ence was found in the expression of IGF -1R mRNA, protein or its phosphorylated form between A 549 and A549/GR cells (P>0.05);while the expression of ERK in A549/GR cells were significantly increased (P<0.05), accompanied with significant up-regulation of mRNA level and phosphorylation level of AKT (P<0.05).The expression of EGFR and its phosphorylated form were significantly reduced in A 549/GR cells as compared with those in A549 cells (P<0.05).Con-clusion EMT and the activation of both AKT and ERK signal pathways may play important roles in acquired EGFR -TKIs-resistance in EGFR wild-type and K-ras mutant NSCLC A549 cells, in which the IGF-1R is not involved .关键词
非小细胞肺癌/表皮生长因子受体-酪氨酸激酶抑制剂/获得性耐药/上皮-间质转化/胰岛素样生长因子Ⅰ型受体Key words
non-small lung cancer/epidermal growth factor receptor -tyrosine kinase inhibitors/acquired drug resistance/epithelial-mesenchymal transition/insulin-like growth factor Ⅰreceptor引用本文复制引用
张曦,张为民,陈蓓,曾云云..IGF-1R信号通路及上皮-间质转化对非小细胞肺癌A549细胞EGFR-TKIs获得性耐药的作用[J].广东医学,2014,(10):1473-1477,5.基金项目
国家自然科学基金面上项目 （）
