HGF increases cisplatin resistance via down-regulation of AIF in lung cancer cells

Am J Respir Cell Mol Biol. 2008 May;38(5):559-65. doi: 10.1165/rcmb.2007-0001OC. Epub 2007 Dec 20.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis Inducing Factor / antagonists & inhibitors
  • Apoptosis Inducing Factor / biosynthesis
  • Apoptosis Inducing Factor / genetics*
  • Cell Line, Tumor
  • Cells, Cultured
  • Cisplatin / pharmacology*
  • Down-Regulation / physiology*
  • Drug Resistance, Neoplasm / physiology*
  • Embryo, Mammalian
  • Fibroblasts / metabolism
  • Focal Adhesion Kinase 1 / metabolism
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / physiology*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Proto-Oncogene Proteins c-met / physiology


  • AIFM1 protein, human
  • Antineoplastic Agents
  • Apoptosis Inducing Factor
  • HGF protein, human
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Cisplatin