Inhibition of angiogenesis as a mechanism for inhibition by Lα-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 of colon carcinogenesis induced by azoxymethane in Wistar rats
✍ Scribed by Kazushige Iseki; Masaharu Tatsuta; Hiroyuki Uehara; Hiroyasu Iishi; Hiroyuki Yano; Noriko Sakai; Shingo Ishiguro
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 57 KB
- Volume
- 81
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The effects of 1␣-hydroxyvitamin D 3 [1␣(OH)D 3 ] and 1,25dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] 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 1␣(OH)D 3 and 1,25(OH) 2 D 3 at lower and higher doses every other day for 45 weeks. Prolonged administration of both 1␣(OH)D 3 and 1,25(OH) 2 D 3 at a higher dose significantly reduced the incidence of colon tumors in week 45. However, administration of 1␣(OH)D 3 or 1,25(OH) 2 D 3 had little or no effect on the histologic type of colon tumors and cancers. Administration of 1␣(OH)D 3 and 1,25(OH) 2 D 3 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 1␣(OH)D 3 and 1,25(OH) 2 D 3 inhibit development of colon tumors. A possible mechanism of inhibition of colon carcinogenesis by 1␣(OH)D 3 and 1,25(OH) 2 D 3 is the inhibition of angiogenesis as well as an anti-proliferative effect.