Susceptibility for NSAIDs-induced apoptosis correlates to p53 gene status in gastric cancer cells

Cancer Invest. 2008 Nov;26(9):868-77. doi: 10.1080/07357900801944872.

Abstract

The anti-tumor effect of non-steroidal anti-inflammatory drugs (NSAIDs) remains unclear. Here, we found that the susceptibility for NSAIDs-induced apoptosis might correlate with the status of the p53 gene in gastric cancer cells. Apoptosis in gastric cancer cells expressing wild-type p53 is induced through up-regulation of bax and down-regulation of bcl-2 and that regulation of the bax-bcl-2 heterodimer may be a major target of NSAIDs. As to gastric cancer cells expressing mutant-type p53, other key factors may exist in the NSAIDs' growth inhibition action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis* / genetics
  • Aspirin / pharmacology
  • Cell Line, Tumor
  • Dimerization
  • Down-Regulation
  • Drug Resistance, Neoplasm*
  • Humans
  • Indomethacin / pharmacology
  • Mutation
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Aspirin
  • Indomethacin