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Inhibition of angiogenesis as a mechanism for inhibition by Lα‐hydroxyvitamin D 3 and 1,25‐dihydroxyvitamin D 3 of colon carcinogenesis induced by azoxymethane in Wistar rats
Author(s) -
Iseki Kazushige,
Tatsuta Masaharu,
Uehara Hiroyuki,
Iishi Hiroyasu,
Yano Hiroyuki,
Sakai Noriko,
Ishiguro Shingo
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990531)81:5<730::aid-ijc11>3.0.co;2-q
Subject(s) - azoxymethane , angiogenesis , medicine , colorectal cancer , endocrinology , vascular endothelial growth factor , gastroenterology , cancer , vegf receptors
The effects of 1α‐hydroxyvitamin D 3 [1α(OH)D 3 ] and 1,25‐dihydroxyvitamin 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 1α(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 1α(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 1α(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 1α(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 1α(OH)D 3 and 1,25(OH) 2 D 3 inhibit development of colon tumors. A possible mechanism of inhibition of colon carcinogenesis by 1α(OH)D 3 and 1,25(OH) 2 D 3 is the inhibition of angiogenesis as well as an anti‐proliferative effect. Int. J. Cancer 81:730–733, 1999. © 1999 Wiley‐Liss, Inc.