HGF increases cisplatin resistance via down-regulation of AlF in lung cancer cells
HGF increases cisplatin resistance via down-regulation of AlF in lung cancer cells
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DOI：
10.1165/rcmb.2007-0001oc
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发表时间：
2008-05-01
影响因子：
6.4
通讯作者：
Chow, Kuan-Chih
中科院分区：
文献类型：
--
作者：
Chen, Jin-Tang;Huang, Chih-Yang;Chow, Kuan-Chih
我们以前的研究表明，晚期肺腺癌（ADC）经常与肝细胞生长因子（HGF）的过度表达有关，HGF具有多能性和抗凋亡活性。在这项研究中，我们研究了HGF对肺ADC细胞凋亡诱导因子（AIF）基因表达和顺铂敏感性的影响。免疫细胞化学和免疫荧光共聚焦显微镜检测AIF的表达。我们的数据显示，加入HGF抑制AIF表达并增加顺铂耐药性。这种作用可能是通过HGF受体及其下游效应子黏着斑激酶（FAK）实现的。有趣的是，FAK基因敲除增加了AIF表达和药物敏感性。另一方面，FAK基因的重新引入恢复了耐药性。提示HGF可能通过c-Met激活FAK、下调AIF表达而诱导顺铂耐药。
Our previous study had shown that advanced stages of lung adenocarcinomas (ADC) was frequently associated with overexpression of hepatocyte growth factor (HGF), which has multipotent and antiapoptotic activities. In this study, we examined the effect of HGF on gene expression of apoptosis-inducing factor (AIF) and cisplatin sensitivity in lung ADC cells. Expression of AIF was determined by immunocytochemistry and confocal immunofluorescence microscopy. Our data show that addition of HGF suppressed AIF expression and increased cisplatin resistance. The effect could be through HGF receptor and its downstream effector, focal adhesion kinase (FAK). Interestingly, knockout of FAK gene increased AIF expression and drug sensitivity. Re-introduction of FAK gene, on the other hand, restored drug resistance. These results suggested that HGF might induce cisplatin resistance via c-Met to activate FAK and down-regulate AIF expression.