1,25-Dihydroxyvitamin D3 Induces N-Myc Downstream Regulated Gene-2 Expression in Papillary Thyroid Carcinoma Cells

Abstract

Purpose: In addition to its role in serum calcium homeostasis, the anti-tumor function of 1,25-dihydroxyvitamin D-3 (calcitriol) in cancer development is well established. N-myc Downstream Regulated Gene 2 which functions as a tumor suppressor gene has recently been shown to be downregulated in various cancer leading to increased tumor incidence, progression and metastasis. The goal of this study was to investigate the possible effects of calcitriol treatment on NDRG2 expression in BCPAP papillary thyroid carcinoma cells. Methods: The experiments were carried on human primary thyroid follicular epithelial cells (Nthy-ori-3-1), and human papillary thyroid carcinoma cells (BCPAP). The half maximal inhibitory concentration (IC 50) of calcitriol on BCPAP cells was determined by WST-1 assay. BCPAP cells were treated with 15 and 30 mu M calcitriol for 24, 48, and 72 hours, respectively. Basal NDGR2 expression in Nthy-ori-3-1 and BCPAP cells as well as the alterations on NDRG2 expression in calcitriol treated BCPAP cells were evaluated with western blot. Results: A significant downregulation of NDRG2 was observed in BCPAP cells when compared to Nthy-ori-3-1 cells (p<0.01). IC50 dose of calcitriol was found to be 64, 54 and 43 mu M for 24, 48 and 72 hours, respectively. NDRG2 protein expression levels were significantly increased in 30 mu M calcitriol treated BCPAP cells after 48 hours (p<0.05). Conclusions: Calcitriol induced NDRG2 protein expression in BCPAP cells. We predict that calcitriol increased NDRG2 protein levels in BCPAP cells via c-Myc repression, which is upregulated by aberrant Wnt/beta-catenin signaling. Further investigation is required to enlighten the possible effect mechanisms of calcitriol in BCPAP cells.