Abstract
Proton beam irradiation promises therapeutic utility in the management of uveal melanoma. Calcitriol (1,25(OH)2D3)—the biologically active metabolite of vitamin D3—and its precursor, calcidiol (25(OH)D3), exert pleiotropic effects on melanoma cells. The aim of the study was to evaluate the effect of both calcitriol and calcidiol on melanoma cell proliferation and their response to proton beam irradiation. Three melanoma cell lines (human SKMEL-188 and hamster BHM Ma and BHM Ab), pre-treated with 1,25(OH)2D3 or 25(OH)D3 at graded concentrations (0, 10, 100 nM), were irradiated with 0–5 Gy and then cultured in vitro. Growth curves were determined by counting the cell number every 24 h up to 120 h, which was used to calculate surviving fractions. The obtained survival curves were analysed using two standard models: linear-quadratic and multi-target single hit. Calcitriol inhibited human melanoma proliferation at 10 nM, while only calcidiol inhibited proliferation of hamster lines at 10 and 100 nM doses. Treatment with either 1,25(OH)2D3 or 25(OH)D3 radio sensitized melanoma cells to low doses of proton beam radiation. The strength of the effect increased with the concentration of vitamin D3. Our data suggest that vitamin D3 may be an adjuvant that modifies proton beam efficiency during melanoma therapy.
Highlights
Because of their high incidence, mortality rates and resistance to the therapy, melanomas are still one the most challenging cancer types for researchers and clinicians [1,2]
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It has been proposed that one of the factors influencing the responsiveness of melanoma cell lines to vitamin D3 is melanin pigmentation [53,54], which would explain the decrease in VDR expression with concomitant decrease in anti-proliferative response to 1,25(OH)2D3 in human melanoma
Summary
Because of their high incidence, mortality rates and resistance to the therapy, melanomas are still one the most challenging cancer types for researchers and clinicians [1,2]. Accumulating evidence from a variety of epidemiological and experimental studies confirms in vitro and in vivo anticancer activity of vitamin D3 [6,7,8,9]. Those studies indicate that biologically active vitamin D3 derivatives may lower the incidence, and inhibit the progression, of various tumours, including melanoma [10,11,12] and sensitize them to radiotherapy [13,14,15,16,17,18]. It was proposed that VDR plays a role in the Sdoevfealro,pnmo esntut daniedsphraovgerebseseionnpoufbmlieslhaendocoynticatcuommobuirnsa[t2i7o]n. of vitamin D3 and proton beam irradiation, a therapySwo iftahr,sunopesrtiuodriedsosheavdeisbtreiebnutpiounblicsohmedpaorneda tcoomphbointaotniornadoifavtiiotanm, winhDic3hainsdcopmromtoonnblyeaumsed in the trieraratmdiaetniot no,f auvtehaelrampyelawniothmasu. pHeoriworevdeors,eredpiostrrtisbuotniotnhecodmiffpearreendcetso inphthoteolnevrealdoiaftiporno,dwuhctiicohnios f free radiccaolsm, mceollnclyyculese, dceilnl mthiegrtaretiaotmn einnht iobfituiovneaal nmdealapnoopmtoa.tiHc soiwgnevaellri,nrgepboerttws eoenntphehodtioffneraenndceps riontothnebeam radiolbteehvteewrlaeoepfnypp[r2ho8od–tuo3cn2t]iaosnnudgopgfreofsrtetoenporbasedsaiimbcalelrsa,ddciifeofltelhrceeyrnaccpleey,s [ci2ne8ll–th3m2e]igesfrufaegticgotenostfinpthhoisebsiiirtbicloeonmdaibfnfiednraeantpicooenpstwiontiitcthhesvigeifntfaaemlcltiniongf D3
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