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Indomethacin decreases EP2 prostanoid receptor expression in colon cancer cells

Hiromichi Fujino1, Xiao-bo Chen, John W Regan

  • 1Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan. fujino@p.chiba-u.ac.jp

Biochemical and Biophysical Research Communications
|June 9, 2007
PubMed

Insights

Nonsteroidal anti-inflammatory drugs may reduce colorectal cancer risk. Indomethacin downregulates EP2 prostanoid receptors in colon cancer cells, suggesting a mechanism beyond cyclooxygenase inhibition.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to decrease colorectal cancer risk.
  • The precise mechanism, particularly whether it solely involves cyclooxygenase (COX) inhibition, remains unclear.

Purpose of the Study:

  • To investigate the effects of indomethacin, a nonselective COX inhibitor, on LS174T human colon cancer cells.
  • To determine if indomethacin's impact on these cells involves mechanisms independent of COX inhibition.

Main Methods:

  • LS174T cells, expressing EP2 prostanoid receptors, were treated with indomethacin.
  • Prostaglandin E(2) (PGE(2))-stimulated cyclic AMP (cAMP) formation, EP2 mRNA expression, and [(3)H]PGE(2) binding were assessed.

Main Results:

  • Indomethacin inhibited PGE(2)-stimulated cAMP formation in a dose-dependent manner (IC(50) = 21 microM).
  • This inhibition correlated with decreased EP2 mRNA expression and reduced specific binding of [(3)H]PGE(2).

Conclusions:

  • Indomethacin treatment leads to the downregulation of EP2 prostanoid receptors in LS174T cells.
  • This downregulation may occur independently of cyclooxygenase (COX) inhibition, suggesting novel anti-cancer pathways for NSAIDs.

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