Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, 65653 Brno, Czech Republic.
Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, Kotlarska 2, 61137 Brno, Czech Republic.
Int J Mol Sci. 2020 Sep 9;21(18):6591. doi: 10.3390/ijms21186591.
The main objective of this study was to analyze changes in the antiproliferative effect of vitamin D3, in the form of calcitriol and calcidiol, via its combined application with all- retinoic acid (ATRA) in osteosarcoma cell lines. The response to treatment with calcitriol and calcidiol alone was specific for each cell line. Nevertheless, we observed an enhanced effect of combined treatment with ATRA and calcitriol in the majority of the cell lines. Although the levels of respective nuclear receptors did not correlate with the sensitivity of cells to these drugs, vitamin D receptor (VDR) upregulation induced by ATRA was found in cell lines that were the most sensitive to the combined treatment. In addition, all these cell lines showed high endogenous levels of retinoic acid receptor α (RARα). Our study confirmed that the combination of calcitriol and ATRA can achieve enhanced antiproliferative effects in human osteosarcoma cell lines in vitro. Moreover, we provide the first evidence that ATRA is able to upregulate VDR expression in human osteosarcoma cells. According to our results, the endogenous levels of RARα and VDR could be used as a predictor of possible synergy between ATRA and calcitriol in osteosarcoma cells.
本研究的主要目的是分析骨肿瘤细胞系中，维生素 D3（骨化三醇和胆钙化醇）与全反式维甲酸（ATRA）联合应用时抗增殖作用的变化。单独使用骨化三醇和胆钙化醇的治疗反应针对每个细胞系都是特异的。然而，我们观察到在大多数细胞系中，ATRA 和骨化三醇联合治疗的效果增强。尽管各核受体的水平与细胞对这些药物的敏感性无关，但在对联合治疗最敏感的细胞系中发现 ATRA 诱导了维生素 D 受体（VDR）的上调。此外，所有这些细胞系均表现出高水平的内源性视黄酸受体 α（RARα）。我们的研究证实，骨化三醇和 ATRA 的联合应用可以在体外增强人骨肉瘤细胞系的抗增殖作用。此外，我们首次提供了证据表明 ATRA 能够上调人骨肉瘤细胞中 VDR 的表达。根据我们的结果，内源性 RARα 和 VDR 水平可作为 ATRA 和骨化三醇在骨肉瘤细胞中可能协同作用的预测因子。
