Nonsteroidal antiinflammatory drugs and progestins synergistically enhance cell death in ovarian epithelial cells

Am J Obstet Gynecol. 2012 Mar;206(3):253.e1-9. doi: 10.1016/j.ajog.2011.11.012. Epub 2011 Nov 25.

Abstract

Objective: There is growing evidence that progestins and nonsteroidal antiinflammatory drugs (NSAIDs) may prevent ovarian cancer. Because both induce apoptosis, we investigated the potential for synergistic impact of combined drug treatment on cell death.

Study design: Using normal and malignant human ovarian epithelial cells and an NSAID-sensitive human colon cancer cell line, we evaluated the effects of progestins and NSAIDs alone and in combination on apoptosis.

Results: Both progestins and NSAIDs dose dependently inhibited cell growth (P < .0001). Doses of NSAIDs or progestins that independently reduced cell viability by less than 30% synergistically reduced cell viability by 70-95% when combined. Similarly, the NSAID/progestin combination conferred 4- to 18-fold (P < .05) increased apoptosis over either treatment alone.

Conclusion: Our results suggest it may be possible to combine progestins and NSAIDs to achieve ovarian cancer prevention at lower doses of each than are required for single administration, thereby lessening the risk of side effects posed by these agents.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Synergism
  • Female
  • Humans
  • Ovarian Neoplasms / prevention & control*
  • Ovary / drug effects*
  • Ovary / pathology*
  • Progestins / administration & dosage
  • Progestins / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Progestins