Vitamin D Deficiency Enhances the Growth of MC-26 Colon Cancer Xenografts in Balb/c Mice

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Abstract
Vitamin D deficiency has been associated with increased risk of colon cancer in epidemiologic and prospective clinical studies. In vitro and in vivo studies demonstrated that 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and its analogs inhibit colon cancer cell proliferation. Few studies have evaluated the effect of vitamin D deficiency on the development and growth of colon cancer. To assess the antiproliferative effects of 25-hydroxyvitamin D [25(OH)D] and 1,25(OH)2D3 in vitro, we cultured MC-26 (a colon cancer cell line) in the presence of 25(OH)D3 and 1,25(OH)2D3 and performed [3H]thymidine incorporation. The proliferation of MC-26 was significantly inhibited by both 25(OH)D3 and 1,25(OH)2D3. To determine the effect of vitamin D deficiency on colon cancer proliferation, Balb/c mice were rendered vitamin D deficient by feeding them a vitamin D–deficient diet for 3 mo. A group of vitamin D–sufficient mice was given the same diet with supplemental vitamin D. The mice were injected with MC-26 colon cancer cells and the tumors were measured daily for 20 d. Vitamin D–sufficient mice had 40% smaller tumors than vitamin D–deficient mice. The tumors were evaluated for mRNA expression of the vitamin D receptor (VDR) and 25-hydroxvitamin D-1α-hydroxylase (1α-OHase) by quantitative RT-PCR. The expression of the mRNA for the VDR and the 1α-OHase was 37- and 6-fold higher, respectively, in the vitamin D–sufficient mice compared with the vitamin D–deficient mice. We conclude that vitamin D deficiency enhances the growth of colon cancer in mice. The tumor expression of VDR and 1α-OHase indicates possible autocrine/paracrine cell growth regulation by vitamin D.

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