Affiliations: Cancer Prevention Division, National Cancer
Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045,
Japan
Note: [] Cancer Prevention Division, National Cancer Center Research
Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. Fax: +81 3
3543 9305; E-mail: kwakabay@gan2.ncc.go.jp
Abstract: 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.
Journal: BioFactors, vol. 12, no. 1-4, pp. 129-133, 2000
