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Non-steroidal anti-inflammatory drugs decrease E2F1 expression and inhibit cell growth in ovarian cancer cells

Blanca L Valle1, Theresa D'Souza, Kevin G Becker

  • 1Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, Maryland, United States of America.

Plos One
|May 3, 2013
PubMed

Insights

Non-steroidal anti-inflammatory drugs (NSAIDs) like diclofenac and indomethacin inhibit ovarian cancer growth. These drugs reduce tumor volume by downregulating the E2F1 pathway, offering potential therapeutic strategies.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Epidemiological studies suggest non-steroidal anti-inflammatory drugs (NSAIDs) reduce cancer risk.
  • NSAIDs show preclinical efficacy in various cancers, but data in ovarian cancer is limited.

Purpose of the Study:

  • To investigate the anti-cancer effects of NSAIDs, specifically diclofenac and indomethacin, in ovarian cancer.
  • To explore the molecular mechanisms underlying NSAID action in ovarian cancer models.

Main Methods:

  • Ovarian cancer cell lines and a xenograft mouse model were used.
  • Cell growth, cell cycle arrest, apoptosis, and tumor volume were assessed.
  • Microarray analysis identified molecular pathways affected by NSAID treatment.

Main Results:

  • Diclofenac and indomethacin inhibited ovarian cancer cell growth by inducing cell cycle arrest and apoptosis.
  • NSAID treatment reduced tumor volume in a xenograft mouse model.
  • Microarray analysis revealed downregulation of E2F1 target genes and E2F1 itself.

Conclusions:

  • NSAIDs, diclofenac and indomethacin, demonstrate anti-proliferative effects in ovarian cancer, both in vitro and in vivo.
  • The anti-cancer effects of NSAIDs in ovarian cancer may be mediated, in part, by the downregulation of the E2F1 pathway.

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