The Influence of Vitamin D Derivatives on the Expression of Apoptotic Genes in Nasal Polyp Fibroblasts

作者：Fraczek Marcin^*; Rostkowska Nadolska Beata; Sliupkas Dyrda Elektra; Kusmierz Dariusz; Pniak Jakub; Latocha Malgorzata

来源：Advances in Clinical and Experimental Medicine, 2010, 19(6): 679-684.

• calcitriol
• tacalcitol
• nasal polyps
• QRT-PCR
• immunohistochemistry
• ELISA
• apoptosis

Background. Vitamin D (VD) modulates the transcription of genes involved in a variety of biological processes, such as phosphocalcic metabolism, proliferation, differentiation, angiogenesis, cell division and cell death. The pro-apoptotic and antiproliferative effects of VD derivates, although still not fully clear, could potentially be harnessed therapeutically.
Objectives. The aim of the paper was to analyze the influence of VD derivatives on the expression of apoptosis associated genes in fibroblasts derived from nasal polyps (NP).
Material and Methods. During routine endonasal surgery 16 NP samples were collected from 5 women and 11 men suffering from chronic rhinosinusitis with NP. The expression of BCL-2 and BAX was detected using RT-PCR and, at the protein level, via ELISA in fibroblast cultures treated with either calcitriol (1,25-(OH)2D3) or tacalcitol (1,24-(OH)2D3) at concentrations of 10(-6)M, 10(-5)M and 10(-4)M each. The comparison group consisted of NP fibroblasts not treated with VD derivatives.
Results.. Both tacalcitol and calcitriol significantly decreased BCL-2 and BAX expression at a concentration of 10(-4)M (p < 0.05). An insignificant decrease in BCL-2/BAK ratios was noted after treatment with both of the examined VD derivatives, regardless of the drug concentration. The highest pro-apoptotic ratio was noted with tacalcitol at a concentration of 10(-5)M. The decrease in the ratio was more a result of inhibited BCL-2 expression than of enhanced BAN expression. Concentration-dependent action was not seen for either of the examined substances.
Conclusions. The results imply that the pro-apoptotic properties of VD derivatives may engage the BCL-2 family pathway only to a limited extent. The slightly better efficiency of tacalcitol in reducing the BCL-2/BAX mRNA ratio, along with its lower calcemic effects, makes tacalcitol preferable to calcitriol (Adv Clin Exp Med 2010, 19, 6, 679-684).

• 出版日期2010-12