湖北医药学院学报2016，Vol.35Issue(6)：536-542,7.DOI:10.13819/j.issn.1006-9674.2016.06.003
冬凌草甲素下调EGFR/ERK/MMP-12和CIP2A/Akt信号通路抑制gefitinib耐受的非小细胞肺癌的转移
Oridonin Inhibits Gefitinib-resistant Non-small-cell Lung Cancer Cells Metastasis by Down-regulating EGFR/ERK/MMP-12 and CIP2A/Akt Signal Pathways
摘要
Abstract
Objective To explore the effects and mechanisms of natural compound oridonin (Ori) inhibit the cells metastasis of gefitinib-resistant non-small cell lung cancer (NSCLC).Methods Lung cancer H1975 cells were treated with different concentrations Ori,then the abilities of migration and inyasion were detected by wound healing assay and transwell assay;Western blot was used to detect the influence of Ori on EGFR and its downstream signal pathway,Akt and correlated prorein expression;gelatin zymography was used to exam the gelatinolytic activity of matrix metalloproteinase-12 (MMP-12);luciferase reporter assay was used to detect the transcription activity of AP-1.Chromatin immunoprecipitation (ChIP) assay was used to test the DNA binding of c-Fos (component of AP-1) to MMP-12 promoter.Results The cells invasion,migration and adhesion were obviously inhibited by Ori;the phosphorylation of EGFR,ERK and Akt,expressions of MMP12 and CIP2A were inhibited by Ori in a dose-dependent manner;but the expression and ability of PP2A weredown-regulated by Ori.The transcription activity of AP-1,DNA binding of c-Fos to MMP-12 promoter were both inhibited by Ori.Conclusion Ori could inhibit the invasion and migration of geftinib-resistant NSCLC cells by down-regulating EGFR/ERK/MMP-12 and CIP2A/PP2A/Akt signal pathways.关键词
冬凌草甲素/gefitinib耐药/肺癌/EGFR/CIP2AKey words
Oridonin/Gefitinib-resistance/Lung cancer/EGFR/CIP2A引用本文复制引用
肖香玲,何中维,黄秋月,季娟丽,张云飞,刘莹..冬凌草甲素下调EGFR/ERK/MMP-12和CIP2A/Akt信号通路抑制gefitinib耐受的非小细胞肺癌的转移[J].湖北医药学院学报,2016,35(6):536-542,7.基金项目
2014年度湖北医药学院优秀中青年科技创新团队资助计划项目(2014 CXX05) （2014 CXX05）
湖北医药学院2015年度研究生启动基金资助计划项目(2015QDJZR16) （2015QDJZR16）
2016年大学生创新创业训练计划项目(201610929001) （201610929001）
