title: Evaluation of a selective prostaglandin E receptor EP1 antagonist for potential properties in colon carcinogenesis.
abstract: BACKGROUND
  Cyclooxygenases (COXs) and prostanoids play pivotal roles in colon carcinogenesis. This study was designed to determine the chemopreventive effects of ONO-8711, a selective prostaglandin E receptor EP1 antagonist, on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats and to compare its potential with that of nimesulide, a well-documented selective COX-2 inhibitor.
  
  
  METHODS
  Five-week-old male F344 rats received s.c. injections of AOM (15 mg/kg body weight) or the saline vehicle once weekly for two weeks and were fed the control diet (AIN-76A) or the experimental diets containing 400 or 800 ppm of ONO-8711 or 400 ppm nimesulide for 5 weeks.
  
  
  RESULTS
  Administration of ONO-8711 at 800 ppm significantly reduced the total number of ACF/colon and 5-bromodeoxyuridine (BrdUrd) labeling index as compared to the control diet group (by 31% and 66%, respectively). As expected, dietary administration of nimesulide also suppressed the development of ACF and BrdUrd labeling index in the colon, by about 39% and 54%, respectively.
  
  
  CONCLUSIONS
  Our finding that ONO-8711 significantly suppresses colonic ACF formation and cell proliferation strengthens the hypothesis that the selective prostaglandin E receptor EP1 antagonists possesses chemopreventive activity against colon cancer development.
authors.affiliation: Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan. tkawamor@gan2.ncc.go.jp
authors.forename: T
authors.initials: T
authors.lastname: Kawamori
authors.forename: N
authors.initials: N
authors.lastname: Uchiya
authors.forename: T
authors.initials: T
authors.lastname: Kitamura
authors.forename: S
authors.initials: S
authors.lastname: Ohuchida
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Maruyama
authors.forename: T
authors.initials: T
authors.lastname: Sugimura
authors.forename: K
authors.initials: K
authors.lastname: Wakabayashi
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001397:Azoxymethane / Q000037:antagonists & inhibitors / Q000633:toxicity; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002208:Caproates / Q000494:pharmacology*; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011451:Prostaglandin-Endoperoxide Synthases; D051381:Rats; D011916:Rats, Inbred F344; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D016588:Anticarcinogenic Agents; D001643:Bridged Bicyclo Compounds; D002208:Caproates; D002273:Carcinogens; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; C122148:ONO 8711; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D001397:Azoxymethane; C012655:nimesulide