MicroRNA-34a overcomes HGF-mediated gefitinib resistance in EGFR mutant lung cancer cells partly by targeting MET
MicroRNA-34a overcomes HGF-mediated gefitinib resistance in EGFR mutant lung cancer cells partly by targeting MET
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MicroRNA-34a 部分通过靶向 MET 克服了 EGFR 突变型肺癌细胞中 HGF 介导的吉非替尼耐药性
DOI：
10.1016/j.canlet.2014.06.010
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发表时间：
2014-09-01
期刊：
影响因子：
9.7
通讯作者：
Zhou, Jian-Ying
中科院分区：
文献类型：
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作者：
Zhou, Jian-Ya;Chen, Xi;Zhou, Jian-Ying
在携带活化表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）中，肝细胞生长因子（HGF）的过表达是通过MET磷酸化恢复PI 3 K/Akt通路活性而对EGFR-酪氨酸激酶抑制剂（TKI）产生获得性耐药的重要机制。在我们的研究中，我们发现miR-34 a的强制表达在HGF诱导的吉非替尼耐药的HCC 827和PC-9细胞中部分地通过靶向MET抑制细胞生长并诱导凋亡。此外，在HGF诱导的吉非替尼耐药小鼠异种移植模型中，在miR-34 a+吉非替尼组中观察到显著的肿瘤消退。这项研究首次证明了miR-34 a在EGFR突变型NSCLC细胞中挽救了HGF诱导的吉非替尼耐药性。(C)2014爱思唯尔爱尔兰有限公司版权所有。
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.