Adenoviral-mediated transfer of p53 gene enhances TRAIL-induced apoptosis in human hepatocellular carcinoma cells

Int J Mol Med. 2004 Aug;14(2):271-5.

Abstract

p53 is a tumor suppressor protein with numerous biological functions including transformation, regulation of cell growth, differentiation and apoptosis. The TNF-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in various transformed cell lines. We investigated the effects of combining wild-type p53 gene transduction by adenoviral infection (Ad-p53) with addition of TRAIL on cell death, expression levels of TRAIL receptors (TRAIL-R1, TRAIL-R2), FLICE inhibitory protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP) on human hepatocellular carcinoma (HCC) cell lines. HCC cell death was increased by combination of Ad-p53 infection and addition of TRAIL compared to either alone. Western blotting demonstrated decreased TRAIL-R1 and TRAIL-R2 levels after infection with Ad-p53. FLIP levels decreased in Huh7 cells and Hep3B cells, and XIAP levels decreased in all three HCC cell lines after infection with Ad-p53. Thus, death of HCC cells due to combined p53 gene transduction and exogenous TRAIL may be due to down regulation of FLIP or XIAP.

MeSH terms

  • Adenoviridae / genetics*
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / therapy
  • Cell Death
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Coloring Agents / pharmacology
  • Down-Regulation
  • Genes, p53*
  • Genetic Therapy / methods
  • Humans
  • Immunoblotting
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Liver Neoplasms / metabolism
  • Membrane Glycoproteins / metabolism*
  • Proteins / metabolism
  • TNF-Related Apoptosis-Inducing Ligand
  • Tetrazolium Salts / pharmacology
  • Thiazoles / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation
  • X-Linked Inhibitor of Apoptosis Protein

Substances

  • Apoptosis Regulatory Proteins
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Coloring Agents
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tetrazolium Salts
  • Thiazoles
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • thiazolyl blue