Suppression of azoxymethane-induced colon cancer development in rats by a prostaglandin E receptor EP1-selective antagonist

Cancer Sci. 2005 May;96(5):260-4. doi: 10.1111/j.1349-7006.2005.00047.x.


Prostaglandin E(2) is involved in colon carcinogenesis through its binding to the PGE(2) receptor subtypes EP(1), EP(2), EP(3) and EP(4). We have demonstrated that administration of ONO-8711, an EP(1)-selective antagonist, suppresses development of AOM-induced ACF in C57BL/6 mice and F344 rats. ONO-8711 also reduced the numbers of intestinal polyps in Min mice. In the present study, we investigated the long-term effects of ONO-8711 on colon cancer development in rats treated with AOM. Male F344 rats were injected subcutaneously with AOM (15 mg/kg body weight) once a week for the first 2 weeks to develop colon cancer. Administration of 400 or 800 p.p.m. ONO-8711 in their diets for 32 weeks reduced the incidence, multiplicity and volume of colon carcinomas. The incidence of colon adenocarcinomas in AOM-treated rats was 97, 83 and 76% (P < 0.05) in the 0, 400 and 800 p.p.m. of ONO-8711 groups, respectively. The multiplicity of adenocarcinomas was also decreased significantly, being 3.31 +/- 0.33, 2.34 +/- 0.27 (P < 0.05) and 2.06 +/- 0.34 (P < 0.01) with 0, 400 and 800 p.p.m. of ONO-8711, respectively. Moreover, treatment with 800 p.p.m. ONO-8711 reduced the mean volume of adenocarcinomas to 49% (P < 0.05) of the value for the AOM treatment alone. Furthermore, the BrdU labeling index was decreased significantly in colon cancer cells by 800 p.p.m. ONO-8711. These results confirm that EP(1) is involved in colon carcinogenesis and that EP(1)-selective antagonists might be promising candidates for colon cancer chemopreventive agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Azoxymethane / pharmacology*
  • Bridged Bicyclo Compounds / pharmacology*
  • Bridged Bicyclo Compounds / therapeutic use
  • Caproates / pharmacology*
  • Caproates / therapeutic use
  • Colonic Neoplasms / chemically induced*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / prevention & control*
  • Male
  • Rats
  • Rats, Inbred F344
  • Receptors, Prostaglandin E / antagonists & inhibitors*
  • Receptors, Prostaglandin E / metabolism
  • Receptors, Prostaglandin E, EP1 Subtype


  • Bridged Bicyclo Compounds
  • Caproates
  • ONO 8711
  • Ptger1 protein, mouse
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP1 Subtype
  • Azoxymethane