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 urg ently needed. The aim of this study was to compare the anti-proliferat ive activity of a new vitamin D-3 analogue, 22-oxa-1,25-dihydroxyvitam in D-3 (22-oxa-calcitriol), on pancreatic cancer cell lines with that of 1,25-dihydroxyvitamin D-3 (calcitriol) with analysis of vitamin D r eceptor status. Methods: Antiproliferative effects of both agents were compared using the (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method and by measuring the tumor size of xenograft inoculate d 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 inhibite d the proliferation (3 of 9 cell lines) and caused a G(1) phase cell c ycle arrest by appearance of numerous domes. In vivo, 22-oxa-calcitrio l inhibited the growth of BxPC-3 xenografts more significantly than ca lcitriol without inducing hypercalcemia. Hs 766T, showing no response to either agent, had the second highest receptor contents with no abno rmalities in its primary structure deduced by receptor complementary D NA. Conclusions: 22-oxa-calcitriol may provide a more useful tool for the chemotherapy of pancreatic cancer than calcitriol. Also, the susce ptibility of the cell lines to both agents is not well determined by e valuating either the contents or the mutation of vitamin D receptor.