| dc.description.abstract | Osteosarcoma (OS) is the most common type of bone cancer in children and adolescents. With the current treatment approaches, the survival rate is
60-70%. Therapies for treating OS have remained the same over the past thirty years. There is a need for developing more effective therapies, which can
significantly improve the survival of the patients who do not respond well to current therapeutic strategies. Epidemiological evidence indicates impaired regulation of cell proliferation and survival appears to be a key event in the etiology of the disease. Previous in vitro and in vivo studies suggest that 1α,25-dihydroxyvitamin D3 (calcitriol or 1,25D) has significant antineoplastic activity by inhibiting cell proliferation and inducing differentiation and apoptosis in breast, prostate, colon, skin, and brain cancer. The molecular mechanisms for
calcitriol-mediated cancer prevention are still unknown. In particular, the role of calcitriol in modulating OS needs to be investigated.
The primary objective of the study was to find out the relationship between calcitriol treatment and expression levels of vitamin D target genes: vitamin D receptor (VDR), 1α-hydroxylase (CYP27B1), 24 hydroxylase (CYP24A1), runt related transcription factor-2 (RUNX-2), and osteocalcin (OCN), by evaluating and comparing the transcription and translation levels of the genes in response to
calcitriol at 3 days, 9 days, as well as 15 days (for gene expression) and 21 days (for protein translation) of cellular growth in OS cell line (143B). The second objective was to rule out the possibility of serum components in masking of any antiproliferative effects of calcitriol by comparing proliferation patterns of OS cell lines cultured in high serum (10%) vs. low serum (1%) and very low serum (0.1%) concentrations in OS 143B, SaOS-2, and U2OS cell lines.
Our preliminary results from this pilot study suggest calcitriol has no significant effect on expression of vitamin D target genes (VDR, CYP27B1, CYP24A1, RUNX-2 and OCN) in 143B OS cell at the mRNA and protein levels,
and exerts no significant anti-proliferative effect in serum-reduced medium in 143B, SaOS-2, and U2OS OS cell lines. | |
