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1α-hydroxyvitamin D3, hypercalcemia, and growth suppression of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors

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Summary

1α-hydroxyvitamin D3 [1α(OH)D3] was administered to female Sprague-Dawley rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. 1α(OH)D3 suppressed the growth of the rat mammary tumors dose-dependently, and in the high dose groups treated with 0.5–1.0µg/kg of 1α(OH)D3, significant inhibition of tumor growth was observed. But daily oral administration of 1α(OH)D3 for four consecutive weeks caused side effects such as hypercalcemia and weight loss. We compared 0.5 µg/kg of 1α(OH)D3 three times weekly with the same dose six times weekly to discover whether or not the side effects can be reduced by treatment schedule. Both groups showed a significant oncostatic effect, compared with the control group, while the side effects were relieved in the three times weekly group. Regarding estrogen receptors (ER) in the tumors, there was no significant difference among the groups. These results suggested that the antitumor effect of 1α(OH)D3 on DMBA-induced mammary tumors was not related to ER status. Combined use of 1α(OH)D3 with 5-fluorouracil (5-FU) or medroxyprogesterone acetate (MPA) was also examined. No significant augmentation of the antitumor effect was seen in the two combinations, although the combined therapy with MPA showed a significant inhibition of weight loss in the rats.

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Authors and Affiliations

  1. Second Department of Surgery, Gunma University School of Medicine, 3-39-15 Showamachi, 371, Maebashi, Japan

    Yuichi Iino, Masao Yoshida, Noritaka Sugamata, Michio Maemura, Susumu Ohwada, Takao Yokoe, Toshikazu Ishikita & Yasuo Morishita

  2. Department of Pharmaceutical Chemistry, Institute of Endocrinology, Gunma University, 371, Maebashi, Japan

    Ryuya Horiuchi

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  1. Yuichi Iino
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  2. Masao Yoshida
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Iino, Y., Yoshida, M., Sugamata, N. et al. 1α-hydroxyvitamin D3, hypercalcemia, and growth suppression of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors. Breast Cancer Res Tr 22, 133–140 (1992). https://doi.org/10.1007/BF01833343

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