Description:
Abstract Vitamin D deficiency has been associated with increased risk of prostate cancer in epidemiologic and prospective studies. An association has also been made between high dietary calcium and increased prostate cancer risk. Previous studies have demonstrated that normal prostate cells and some prostate cancer cells have the ability to convert 25(OH)D to 1α,25(OH)2D. This ability along with epidemiological evidence correlating an inverse relationship between serum 25(OH)D levels and prostate cancer risk suggests that vitamin D may be important for prostate cancer prevention. The effect of dietary vitamin D and calcium on the growth of human androgen-insensitive prostate tumor in an athymic mouse model was evaluated. Three factors were considered in evaluating the role of dietary calcium and vitamin D on prostate tumor in our mice model: tumor-growth, elevation of serum calcium and overall growth of the animals (body weight). Immunohistochemical staining and Real Time PCR analysis were performed on tumors to elucidate the molecular mechanism(s) involved in vitamin D regulation of prostate cancer. Tumor-growth was highest in normal calcium, vitamin D deficient diet group (381±59 mm3) while growth in normal calcium, vitamin D sufficient (179±36 mm3), high calcium, vitamin D sufficient (199±25 mm3) and deficient (204±43 mm3) diets were not significantly different from one another. The normal calcium, vitamin D deficient diet had mice that were normo-calcemic compared to the other diet groups though there was no significant difference between groups for the weights of the animals. Proliferative (Ki67) and apoptotic (Caspase 3) staining revealed no significant difference between vitamin D sufficient and deficient diet groups. Additional staining for p21 did not show any difference among the diet groups. Gene analysis for p21, p27 and p53 did not demonstrate altered transcriptional activity in vitamin D sufficient groups. Bax and bcl-2 mRNA expression were both increased in the high calcium, vitamin D deficient diet group. The difference in tumor growth between the normal calcium, vitamin D deficient diet and the other diets suggest an important role of dietary vitamin D as a preventive agent in androgen-insensitive prostate cancer. More in vivo studies are needed to understand the molecular mechanism(s) behind vitamin D's antitumorigenic effects. Citation Format: Rahul Ray, Mara Banks, Hilal Abuzahra, Kelly S. Persons, Vikram J. Eddy, James R. Lambert, Michael F. Holick. Effect of dietary vitamin D3 and calcium on the growth of androgeninsensitive human prostate tumor in a murine model [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A41.