Effect of 22-oxa-1,25-dihydroxyvitamin D-3 on human thyroid cancer cell growth

To examine whether synthetic vitamin D-3 analog, 22-oxa-1,25(OH)(2)D-3 (OCT ) has an inhibitory effect on the growth of thyroid carcinoma, we tested th e in vitro and in vivo effects of OCT on the growth of a well-differentiate d thyroid cancer cell line, NPA. OCT bound to its receptor at the same rate as 1,25(OH)(2)D-3, and inhibited the proliferation of NPA cells in vitro i n a dose-dependent manner, similar to that observed with 1,25 (OH)2D3 North ern blot analysis showed that steady-state and fetal bovine serum-stimulate d levels of c-myc mRNA were suppressed after 0.5-4 hour treatment with OCT. Transfection studies with the deletion mutants of the 5'-up-stream flankin g region of c-myc/chroramphenicol acetyltransferase chimera genes indicated the presence of an OCT responsive element between -410 and -106. Next, we examined OCT effects in implanted NPA tumor cells in nude mice. OCT showed no remarkable hypercalcemic effect compared to 1, 25 (OH2)D-3, but OCT and 1, 25 (OH2)D-3, had no significant inhibitory effect in vivo after either i ntra-tumor or intra-peritoneum injection. Our results demonstrate that OCT inhibits the proliferation of well-differentiated thyroid cancer in an in v itro system associated with the suppression of c-myc mRNA, but this inhibit ory effect was not reproducible in in vivo model.