[Correlation between the concentration of 1,25 alpha dihydroxyvitamin D3 receptors and growth inhibition, and differentiation of human osteosarcoma cells induced by vitamin D3].
It has been previously reported that several human cancer cell lines possess specific receptors for 1,25-dihydroxyvitamin D3. In the present study, the concentration of the 1 alpha,25 dihydroxyvitamin D3 receptors has been determined in four human osteosarcoma cell lines--MG63, OST, MNNG-HOS, and KHOS-NP, and we report the effect of 1 alpha, 25 dihydroxyvitamin D3 on these cells. The concentration of 1 alpha, 25 dihydroxyvitamin D3 receptors in MG63, OST, MNNG-HOS and KHOS-NP was 31.1, 12.1, 5.9 and 3.0 fmol/mg of cytosol protein, respectively. These cell lines were classified into two groups according to the concentration of the receptors. The two receptor-rich cell lines were MG63 and OST, and the receptor-poor cell lines were MNNG-HOS and KHOS-NP. In a colony-forming assay, 1 alpha, 25 dihydroxyvitamin D3 (10(-8)M, 10(-9)M) was found to significantly suppress the growth of the receptor-rich cell lines (p < 0.01), but did not suppress that of the receptor-poor cell lines. In an antitumor assay, athymic mice received a transplantation of tumor cells and were treated with 2.5 nmol/kg of 1 alpha hydroxyvitamin D3. Then the relative mean weight of the tumor was measured (MG63 was, however, not transplantable into athymic mice.) As a result, 1 alpha hydroxyvitamin D3 was found to have significantly suppressed the relative mean tumor weight of OST and MNNG-HOS compared with a control group (p < 0.05), but did not suppress that of KHOS-NP. Histologically, 1 alpha hydroxyvitamin D3 induced marked chondrogenetic differentiation in OST alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Tokuumi
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Department of Orthopaedic Surgery, School of Medicine, Kanazawa University, Japan.
D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D018167:Receptors, Calcitriol / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018167:Receptors, Calcitriol; D002762:Cholecalciferol