Correlation between VDR expression and antiproliferative activity of vitamin D3 compounds in combination with cytostatics.
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.
Pelczynska
Marzena
M
Department of Experimental Oncology, Institute of Immunology and Experimental Therapy, 12 R. Weigla St., 53-114 Wroclaw, Poland.
Wietrzyk
Joanna
J
Jaroszewicz
Iwona
I
Nevozhay
Dmitry
D
Switalska
Marta
M
Kutner
Andrzej
A
Zabel
Maciej
M
Opolski
Adam
A
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004100:Dihydroxycholecalciferols / Q000008:administration & dosage / Q000494:pharmacology*; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D007150:Immunohistochemistry; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D018167:Receptors, Calcitriol / Q000096:biosynthesis* / Q000378:metabolism
D004100:Dihydroxycholecalciferols; D018167:Receptors, Calcitriol; C023850:1 alpha,24-dihydroxyvitamin D3; D004317:Doxorubicin; D002117:Calcitriol; D002945:Cisplatin