Hepatocyte growth factor and HER2eu downregulate expression of apoptosis-inducing factor in non-small cell lung cancer

摘要

Our previous study showed that patients with advanced stages of non-small cell lung cancer (NSCLC) were frequently detected with upregulation of hepatocyte growth factor (HGF). In vitro, HGF reduced expression of apoptosis-inducing factor (AIF) and cisplatin sensitivity in NSCLC cells. The effect of HGF was via HGF receptor (c-MET) and the downstream effector, focal adhesion kinase (FAK). In this study, we determined the prognostic value of AIF in NSCLC patients. AIF expression was determined by immunohistochemistry and immunoblotting. Our data show that AIF expression was associated with better prognosis. Expression of AIF inversely correlated with that of positive NSCLC markers, e.g., dihydrodiol dehydrogenase (DDH), c-MET, short oncostatin M receptor (OSMRs), matrix metalloproteinase (MMP)-1, and HER2eu, which were closely associated with drug resistance, tumor recurrence, metastasis and poor prognosis. Noteworthy, silence of HER2eu gene expression increases AIF level and drug sensitivity. Addition of HGF inhibits AIF expression in HER2eu-silenced cells. These results suggested that both HGF and HER2eu affect drug resistance by regulating AIF expression in NSCLC.