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. MATERIALS AND 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. CONCLUSION: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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Kawamori T,Uchiya N,Kitamura T,Ohuchida S,Yamamoto H,Maruyama T,Sugimura T,Wakabayashi K

subject

Has Abstract

pub_date

2001-11-01 00:00:00

pages

3865-9

issue

6A

eissn

0250-7005

issn

1791-7530

journal_volume

21

pub_type

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