Inhibitory effect of 22-oxa-1,25-dihydroxyvitamin D-3 on the proliferation of pancreatic cancer cell lines

Background & Aims: Effective chemotherapy for pancreatic cancer is urgently needed. The aim of this study was to compare the anti-proliferative activity of a new vitamin D-3 analogue, 22-oxa-1,25-dihydroxyvitamin D-3 (22-oxa-calcitriol), on pancreatic cancer cell lines with that of 1,25-dihydroxyvitamin D-3 (calcitriol) with analysis of vitamin D receptor status. Methods: Antiproliferative effects of both agents were compared using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method and by measuring the tumor size of xenograft inoculated into athymic mice. Vitamin D receptor contents by Scatchard analysis and mutational analysis of receptor complementary DNA were performed. Results: In vitro, 22-oxa-calcitriol and calcitriol markedly inhibited the proliferation (3 of 9 cell lines) and caused a G(1) phase cell cycle arrest by appearance of numerous domes. In vivo, 22-oxa-calcitriol inhibited the growth of BxPC-3 xenografts more significantly than calcitriol without inducing hypercalcemia. Hs 766T, showing no response to either agent, had the second highest receptor contents with no abnormalities in its primary structure deduced by receptor complementary DNA. Conclusions: 22-oxa-calcitriol may provide a more useful tool for the chemotherapy of pancreatic cancer than calcitriol. Also, the susceptibility of the cell lines to both agents is not well determined by evaluating either the contents or the mutation of vitamin D receptor.