1α,25-Dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol, a Noncalcemic Analogue of 1α,25-Dihydroxyvitamin D3, Inhibits Azoxymethane-induced Colonic Tumorigenesis

摘要: Abstract Vitamin D 3 and its metabolites, particularly 1α,25-dihydroxyvitamin (1α, 25(OH) 2 ), have received increasing attention as potential anti-carcinogens in the prevention of cancers a number organs, including colon. These agents, however, to induce hypercalcemia, thus limiting their practical use for these purposes. In present studies it was, therefore, interest determine whether dietary supplementation with 1α,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecal-ciferol (RO24-5531), recently synthesized apparently noncalcemic analogue 1α,25(OH) , inhibited colon cancer induced by azoxymethane (AOM). Rats were placed on standard diet or fed this supplemental RO24-5531 (2.5 nmol/kg feed) before during (initiation arm), after AOM vehicle administration (postinitiation arm). After 34 weeks study, animals each group sacrificed, colons removed examined macroscopically microscopically presence tumors. At time sacrifice, animals9 serum calcium, phosphorus, 25-hydroxyvitamin levels also analyzed. The results demonstrated that initiation arm experiments significantly reduced (by 70%) incidence AOM-induced colonic tumors compared rats without RO24-5531. Moreover, regimen abolished development adenocarcinomas model. Although there was trend postinitiation study reduce tumors, did not reach statistical significance ( P > 0.05). addition, neither influenced rates growth . studies, demonstrate first is chemopreventive agent model experimental carcinogenesis. They suggest may ultimately prove useful clinical trials.