MicroRNA-34a overcomes HGF-mediated gefitinib resistance in EGFR mutant lung cancer cells partly by targeting MET

被引：120

作者：

Zhou, Jian-Ya ^{[1
]}

Chen, Xi ^{[1
]}

Zhao, Jing ^{[2
]}

Bao, Zhang ^{[1
]}

Chen, Xing ^{[1
]}

Zhang, Pei ^{[1
]}

Liu, Zhen-Feng ^{[3
]}

Zhou, Jian-Ying ^{[1
]}

机构：

[1] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Resp Dis,Thorac Dis Diag & Treatment Ctr, Hangzhou 310003, Zhejiang, Peoples R China

[2] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Pathol, Hangzhou 310003, Zhejiang, Peoples R China

[3] Zhejiang Univ, Sch Med, Affiliated Hosp 1, PET Ctr, Hangzhou 310003, Zhejiang, Peoples R China

来源：

CANCER LETTERS | 2014年 / 351卷 / 02期

基金：

中国国家自然科学基金;

关键词：

miR-34a; Lung cancer; HGF; MET; Gefitinib resistance; HEPATOCYTE GROWTH-FACTOR; FACTOR RECEPTOR; C-MET; ADENOCARCINOMA; METASTASIS; EXPRESSION; MIR-34A; CHEMOTHERAPY; METHYLATION; MUTATION;

D O I：

10.1016/j.canlet.2014.06.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

In non-small-cell lung cancer (NSCLC) that harbours an activating epidermal growth factor receptor (EGFR) mutation, over-expression of hepatocyte growth factor (HGF) is an important mechanism involved in the acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) by restoring activity of the PI3K/Akt pathway via phosphorylation of MET. In our study, we found that the forced expression of miR-34a inhibited cell growth and induced apoptosis partly by targeting MET in HGF-induced gefitinib-resistant HCC827 and PC-9 cells. Furthermore, dramatic tumour regression was observed in the miR-34a plus gefitinib group in HGF-induced gefitinib resistant mouse xenograft models. This study demonstrates for the first time that miR-34a rescues HGF-induced gefitinib resistance in EGFR mutant NSCLC cells. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

引用

页码：265 / 271

页数：7

共 37 条

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