胞外信号调节激酶通路活化促进埃克替尼耐药的非小细胞肺癌侵袭和转移

Activation of extracellular signal-regulated kinase pathway promotes the invasion and metastasis of icotinib-resistant non-small cell lung cancer

目的研究胞外信号调节激酶(ERK)通路与埃克替尼耐药的非小细胞肺癌侵袭和转移的关系。方法将PC9细胞持续暴露于埃克替尼中并逐渐增加药物浓度,筛选并建立耐药细胞系,MTT法检测PC9和PC9/IcoR细胞增殖能力,Transwell迁移实验和基质胶侵袭实验检测PC9和PC9/IcoR细胞迁移和侵袭能力,Western blotting检测ERK、phosph-ERK、EGFR、phosph-EGFR的蛋白表达。结果与PC9细胞相比,PC9/IcoR细胞迁移和侵袭能力明显增强。PC9/IcoR细胞中EGFR和ERK的磷酸化水平明显升高。PD98059抑制ERK活化后,PC9/IcoR细胞迁移和侵袭能力明显下降。结论ERK通路活化促进了埃克替尼耐药的非小细胞肺癌细胞转移。

Objective To investigate the relationship between the extracellular signal-regulated kinase(ERK)pathway and the invasion and metastasis of icotinib-resistant non-small cell lung cancer.Methods An icotinib-resistant cell line was screened and established from PC9 cells that were continuously exposed to increasing concentrations of icotinib.The proliferation of PC9 and PC9/IcoR(PC9 icotinibresistant)cells was analyzed using the MTT assay.The migration and invasion abilities of these two cell lines were estimated using the Transwell and Matrigel invasion assays.The expression levels of proteins such as ERK,phospho-ERK,EGFR,and phospho-EGFR were detected using Western blotting.Results The migration and invasion abilities of PC9/IcoR cells were significantly enhanced compared to those of PC9 cells,along with the expression levels of phospho-EGFR and phospho-ERK.However,PD98059-mediated inhibition of ERK activation led to a significant decrease in the migration and invasion abilities of PC9/IcoR cells.Conclusion The activation of the ERK pathway promotes the metastasis of icotinib-resistant non-small cell lung cancer cells.