Preliminary Study On Nonclassic Actions Of Vitamin D

Vitamin D plays a central role in calcium and phosphate homeostasis for normal development and maintenance of bone. The biological effects of active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] are mediated by a high-affinity receptor that acts as a ligand-activated transcription factor. The VDR was found originally in the classic vitamin D target organs involved in mineral homeostasis: the intestine, bone, kidney, and the parathyroid glands. More recently, the VDR has been detected in many other tissues and cell types as well. These vitamin D target organs respond to 1,25(OH)2D3 with diverse biological actions including immunomodulation, the control of other hormonal systems, inhibition of cell growth, and induction of cell differentiation. These nonclassic actions have raised a number of new therapeutic applications of 1,25(OH)2D3 to immune dysfunction (autoimmune disease), endocrine disorders (hyperparathyroidism), and hyperproliferative disorders (leukemia, cancer, psoriasis).Objective: To explore the nonclassic role of vitamin D such as the therapeutic potential of 1,25(OH)2D3 in the treatment of ovarian cancer, the radioprotective and anti-inflammatory effects.Methods: (1) The ovarian cancer cell line SKOV3 was treated with different concentrations of 1,25(OH)2D3 and carboplatin. Cell viability was determined by MTT assay. SKOV3 cell cycle was analyzed by the flow cytometry (FCM) following staining of cells with propidium iodide (PI). (2) Mice were treated with vitamin D (Alfacalcidol Soft Capsules) by gavage and were exposed to 60Coγ-rays at the dose of 6.0Gy. Peripheral blood cell count was analyzed by autoanalyzer. Micronucleated polychromatic erythrocytes (PCE) in bone marrow were counted under a microscope. (3) 1α-hydroxylase gene knock out mice were treated with lipopolysaccharide (LPS) and the peritoneal macrophages were cultured in vitro. The inflammatory cytokines NO and TNF-αproduced were detected by the greiss and enzyme-linked immunosorbent assay (ELISA).Result: (1) 1,25(OH)2D3 inhibited SKOV3 cell growth which arrested in G2/M phase.1,25(OH)2D3 and CBP produced a agonistic action on cell growth inhibition when treated at the same time, but showed an antagonistic action when treated in different orders. (2) Vitamin D treatment facilitated the recovery of white blood cell counting following radiation exposure, and significantly decreased bone marrow PCE micronucleus rate induced by radiation. FCM analysis showed that the G2 and S phases of bone marrow cells(BMC) in vitamin D-treated group increased significantly 24h after the irradiation. (3) Both LPS-induced macrophage inflammatory cytokines (TNF-αand NO) and mortality in 1α-hydroxylase gene knockout mice were significantly increased in comparison with the wide type mice.Conclusion: (1) 1,25(OH)2D3 could inhibit the SKOV3 cell growth in a dose-response manner, with an additive joint action when combined with CBP.(2) 1,25(OH)2D3 was a potential radioprotective agent.(3) 1,25(OH)2D3 displayed an anti-inflammatory effect.