alpha-Fetoprotein shields hepatocellular carcinoma cells from apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand

Cancer Lett. 2007 May 8;249(2):227-34. doi: 10.1016/j.canlet.2006.09.004. Epub 2006 Oct 13.

Abstract

The interference of alpha-fetoprotein (AFP) with the apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in Bel 7402 cells was investigated in the current study. The results showed a moderate degree of drug-resistance of Bel 7402 cells to TRAIL. The caspase-3 cascade was the main pathway involved in TRAIL-induced apoptosis, which was virtually abolished in the presence of AFP. TRAIL together with antibody against AFP was able to accelerate the death of tumor cells. This study suggests the possibility a therapeutic strategy for improving clinical treatment of liver tumor with TRAIL could be effected through antagonizing the shelter effect of AFP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antimetabolites, Antineoplastic / pharmacology
  • Apoptosis / drug effects*
  • Carcinoma / drug therapy
  • Carcinoma / metabolism
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Fluorouracil / pharmacology
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Neoplasm Proteins / metabolism
  • Proteins / pharmacology*
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand*
  • alpha-Fetoproteins

Substances

  • AFP protein, human
  • Antibodies, Monoclonal
  • Antimetabolites, Antineoplastic
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Proteins
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • alpha-Fetoproteins
  • Caspase 3
  • Fluorouracil