Correlation between VDR expression and antiproliferative activity of vitamin D3 compounds in combination with
Marzena Pelczynska1, Joanna Wietrzyk, Iwona Jaroszewicz
1Department of Experimental Oncology, Institute of Immunology and Experimental Therapy, 12 R. Weigla St., 53-114 Wroclaw, Poland.
Abstract:
Calcitriol is a potent antiproliferative agent against various tumour cells in vitro. Its biological activity is mediated by the vitamin D receptors (VDRs). Here, we present the results of a study on vitamin D3 compounds (calcitriol and its analogue PRI-2191) as potential agents in combined antitumour therapy in vitro. Applying antiproliferative SRB and MTT assays, we measured the growth inhibitory effects of vitamin D compounds applied alone or in combination with either cisplatin or doxorubicin. Next, we examined the correlation of this effect with the presence of nVDR (nuclear VDR). The following cancer cell lines were applied: HL-60 (human leukaemia), SW707 (human colon cancer), A549 (human lung cancer), WEHI-3 (mouse leukaemia). The treatment of tumour cells with the combination of vitamin D compounds and cytostatics decreased the inhibitory concentration 50% (IC50) values compared with the effects of cytostatics applied alone. The synergistic effect was positively correlated with nVDR expression.
Insights
Vitamin D3 compounds, including calcitriol, enhance chemotherapy by reducing required doses against cancer cells. This synergistic effect is stronger when cancer cells express nuclear vitamin D receptors (nVDR).
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Calcitriol exhibits antiproliferative properties against diverse tumor cells.
- The biological activity of calcitriol is mediated through vitamin D receptors (VDRs).
Purpose of the Study:
- To investigate vitamin D3 compounds (calcitriol and PRI-2191) as potential adjuncts in combined antitumour therapy.
- To assess the synergistic effects of vitamin D3 compounds with cisplatin or doxorubicin.
- To correlate the observed antitumour effects with nuclear VDR (nVDR) expression.
Main Methods:
- Utilized antiproliferative SRB and MTT assays to measure growth inhibition.
- Tested vitamin D3 compounds alone and in combination with cytostatics (cisplatin, doxorubicin).
- Examined effects across human (HL-60, SW707, A549) and mouse (WEHI-3) cancer cell lines.
Main Results:
- Combined treatment with vitamin D3 compounds and cytostatics significantly reduced the inhibitory concentration 50% (IC50) values compared to cytostatics alone.
- The synergistic antitumour effect was positively correlated with the expression of nuclear VDR (nVDR).
Conclusions:
- Vitamin D3 compounds demonstrate potential as synergistic agents in combined cancer therapy.
- The efficacy of combined therapy is dependent on the expression levels of nuclear VDR in tumor cells.
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