Abstract
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-trans 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.
Highlights
Osteosarcoma is a high-grade primary mesenchymal tumor characterized by spindle cells depositing an immature osteoid matrix [1]
The levels of respective nuclear receptors did not correlate with the sensitivity of cells to these drugs, vitamin D receptor (VDR) upregulation induced by all-trans retinoic acid (ATRA) was found in cell lines that were the most sensitive to the combined treatment
We focused on the possible effects of calcitriol and calcidiol alone or in combination with ATRA in patient-derived osteosarcoma cell lines, with special regard to the mechanism of interaction between calcitriol and ATRA
Summary
Osteosarcoma is a high-grade primary mesenchymal tumor characterized by spindle cells depositing an immature osteoid matrix [1]. Osteosarcoma is the most frequent primary malignancy of bone in children and the most frequent primary malignancy in adolescents apart from leukemia and lymphoma [2,3]. For patients with high-grade tumors, other therapeutic methods, such as chemotherapy and radiotherapy, must be employed [5]. Chemotherapy used in osteosarcoma protocols remains essentially unchanged since the introduction of high-dose methotrexate, doxorubicin, and cisplatin in the late 1970s [6,7,8]. The five-year overall survival has remained approximately 60% over the last five decades; the overall survival of patients with metastatic osteosarcoma is
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
