HGF increases cisplatin resistance via down-regulation of AIF in lung cancer cells.
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 anti-apoptotic 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.
Chen
Jin-Tang
JT
Graduate Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo-Kuang Road, Taichung, 40227 Taiwan.
Huang
Chih-Yang
CY
Chiang
Yung-Yen
YY
Chen
Wen-Heng
WH
Chiou
Shiow-Her
SH
Chen
Chih-Yi
CY
Chow
Kuan-Chih
KC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051033:Apoptosis Inducing Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D019859:Proto-Oncogene Proteins c-met / Q000502:physiology
C494829:AIFM1 protein, human; D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D002945:Cisplatin