Effect of hepatocyte growth factor (HGF) on the level of Survivin & XIAP expression in several human cancer cell lines, after treating with DNA damaging agent

Mol Cell Biochem. 2007 Oct;304(1-2):199-205. doi: 10.1007/s11010-007-9500-z. Epub 2007 May 30.

Abstract

Hepatocyte growth factor (HGF) has opposite biological activities in regulating apoptosis, also underlying molecular mechanisms are not clearly defined. We investigated HGF ability to inhibit cell death, which was induced by Doxorubicin, a DNA damaging agent. Also Survivin and XIAP mRNA levels were compared in HGF treated and non-treated cells. Cell proliferation and death were assessed using MTT assay and dye exclusion tests. Quantitative real-time PCR was used to evaluate Survivin and XIAP expression levels after treatment with HGF. ELISA was performed to quantify HGF secretion in the selected cancer cell lines media. HGF appeared to have inhibitory effect on Doxorubicin induced cell death in all of the studied cell lines. It had minimal effect on XAIP and Survivin expression levels in MRC-5, MOLT-4 and AGS cell lines; except for XIAP expression level in AGS cell line, which was increased substantially after treatment. Surprisingly, in KG-1 cell line, XIAP and Survivin expression levels were significantly reduced after HGF treatment. Although several members of IAP gene family are reported to play role in HGF mediated cytoprotective pathway, we showed that XIAP and Survivin do not seem to be involved.

MeSH terms

  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cytoprotection / drug effects
  • Cytotoxins / pharmacology*
  • DNA Damage / genetics*
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hepatocyte Growth Factor / pharmacology*
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins / genetics*
  • Neoplasm Proteins / genetics*
  • Neoplasms / pathology*
  • Survivin
  • X-Linked Inhibitor of Apoptosis Protein / genetics*

Substances

  • BIRC5 protein, human
  • Cytotoxins
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Survivin
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • Hepatocyte Growth Factor
  • Doxorubicin