Vitamin D deficiency enhances the growth of MC-26 colon cancer xenografts in Balb/c mice.
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-1alpha-hydroxylase (1alpha-OHase) by quantitative RT-PCR. The expression of the mRNA for the VDR and the 1alpha-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 1alpha-OHase indicates possible autocrine/paracrine cell growth regulation by vitamin D.
Tangpricha
Vin
V
Division of Endocrinology, Diabetes and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Spina
Catherine
C
Yao
Min
M
Chen
Tai C
TC
Wolfe
M Michael
MM
Holick
Michael F
MF
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000818:Animals; D002117:Calcitriol / Q000097:blood / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D018167:Receptors, Calcitriol / Q000235:genetics; D014183:Transplantation, Heterologous; D014808:Vitamin D Deficiency / Q000503:physiopathology*; D014815:Vitamins / Q000097:blood / Q000494:pharmacology*
D018167:Receptors, Calcitriol; D014815:Vitamins; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol