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COX‐2 and iNOS, good targets for chemoprevention of colon cancer
Author(s) -
Watanabe Kouji,
Kawamori Toshihiko,
Nakatsugi Seiichi,
Wakabayashi Keiji
Publication year - 2000
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520120120
Subject(s) - colorectal cancer , medicine , cancer research , cancer , oncology
Cyclooxygenase (COX)‐2 has been suggested to play an important role in colon carcinogenesis. We found that the COX‐2 selective inhibitor, nimesulide, reduces azoxymethane (AOM)‐induced aberrant crypt foci (ACF) in rats and colon carcinogenesis in mice, as well as formation of intestinal polyps in Min mice. Thus, selective inhibitors of COX‐2, which catalyzes the synthesis of prostanoids, could be good candidates as chemopreventive agents against colon cancer. Examination of the effect of prostanoid receptor deficiency and a selective antagonist of prostanoid receptor on the development of AOM‐induced ACF in mice revealed the involvement of the EP_1 receptor. Moreover, a selective EP_1 antagonist reduced the number of intestinal polyps in Min mice. These results suggest that PGE_2 contributes to colon carcinogenesis through binding to the EP_1 receptor. Nitric oxide synthase (NOS) is known to be overexpressed in colon cancers of humans and rats, and a NOS inhibitor, L‐N G ‐nitroarginine methyl ester, was found to inhibit the development of AOM‐induced ACF in rats. Thus, NOS including iNOS could also be a good target for chemoprevention of colon cancer, as in the COX‐2 case.