Effect of 22-oxa-1,25-dihydroxyvitamin D3 on human thyroid cancer cell growth.
To examine whether synthetic vitamin D3 analog, 22-oxa-1,25(OH)2D3 (OCT) has an inhibitory effect on the growth of thyroid carcinoma, we tested the in vitro and in vivo effects of OCT on the growth of a well-differentiated thyroid cancer cell line, NPA. OCT bound to its receptor at the same rate as 1,25(OH)2D3, and inhibited the proliferation of NPA cells in vitro in a dose-dependent manner, similar to that observed with 1,25 (OH)2D3. Northern blot analysis showed that steady-state and fetal bovine serum-stimulated 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 flanking region of c-myc/chloramphenicol 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)D3, but OCT and 1, 25 (OH2)D3, had no significant inhibitory effect in vivo after either intra-tumor or intra-peritoneum injection. Our results demonstrate that OCT inhibits the proliferation of well-differentiated thyroid cancer in an in vitro system associated with the suppression of c-myc mRNA, but this inhibitory effect was not reproducible in in vivo model.
Okano
K
K
Department of Orthopaedic Surgery, Nagasaki University School of Medicine, Japan.
Usa
T
T
Ohtsuru
A
A
Tsukazaki
T
T
Miyazaki
Y
Y
Yonekura
A
A
Namba
H
H
Shindoh
H
H
Yamashita
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D016259:Genes, myc; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018167:Receptors, Calcitriol / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018167:Receptors, Calcitriol; D004247:DNA; D002117:Calcitriol; C051883:maxacalcitol