Inhibition of angiogenesis as a mechanism for inhibition by 1alpha-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 of colon carcinogenesis induced by azoxymethane in Wistar rats.

The effects of 1alpha-hydroxyvitamin D3[1alpha(OH)D3] and 1,25-dihydroxyvitamin D3[1,25(OH)2D3] on the incidence of colon tumors induced by azoxymethane and on the labeling index and angiogenesis of colon tumors were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body weight of azoxymethane and i.p. injections of 1alpha(OH)D3 and 1,25(OH)2D3 at lower and higher doses every other day for 45 weeks. Prolonged administration of both 1alpha(OH)D3 and 1,25(OH)2D3 at a higher dose significantly reduced the incidence of colon tumors in week 45. However, administration of 1alpha(OH)D3 or 1,25(OH)2D3 had little or no effect on the histologic type of colon tumors and cancers. Administration of 1alpha(OH)D3 and 1,25(OH)2D3 at higher doses significantly decreased the labeling index, the immuno-histochemical staining for vascular endothelial growth factor and microvessel counts in colon tumors. Our findings suggest that both 1alpha(OH)D3 and 1,25(OH)2D3 inhibit development of colon tumors. A possible mechanism of inhibition of colon carcinogenesis by 1alpha(OH)D3 and 1,25(OH)2D3 is the inhibition of angiogenesis as well as an anti-proliferative effect.