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Differentiating and antitumor activities of 1α,25‐dihydroxyvitamin D 3 in vitro and 1α‐hydroxyvitamin D 3 in vivo on human osteosarcoma
Author(s) -
Tsuchiya Hiroyuki,
Morishita Hajime,
Tomita Katsuro,
Ueda Yoshimichi,
Tanaka Motohiro
Publication year - 1993
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.1100110114
Subject(s) - osteosarcoma , in vivo , alkaline phosphatase , in vitro , cell culture , chemistry , mtt assay , microbiology and biotechnology , endocrinology , medicine , biology , biochemistry , cancer research , enzyme , genetics
Abstract The differentiating and antitumor activities of 1α,25‐dihydroxyvitamin D 3 (1α,25(OH) 2 D 3 ) in vitro and 1α‐hydroxyvitamin D 3 (1α(OH)D 3 ) in vivo were studied with a human osteosarcoma cell line (OST strain). Antitumor activity was estimated with the use of 3‐(4,5‐dimethylthiazol)‐2, 5‐diphenyltetrazolium bromide (MTT) assay, colony‐forming assay, and athymic mouse assay. The intracellular alkaline phosphatase (ALP) activity of tumor cells and production of bone Gla protein (BGP) in culture media were measured to mark osteoblastic differentiation. In addition, the combination of 1α,25(OH) 2 D 3 and cis‐dichlorodiammineplatinum(II) (CDDP) was tested by the colony‐forming assay and the measurement of ALP activity and BGP production for differentiating and antitumor effects. The assays revealed that 1α,25(OH) 2 D 3 exerted a dose‐related, growth‐inhibitory influence. In the colony‐forming assay, the 1α,25(OH) 2 D 3 ‐treated colonies were smaller than the untreated colonies. The ALP activity and the BGP production also increased in relation to dose. In the assay in athymic mice, the relative weight of tumors treated with 1α(OH)D 3 at 2.5 nmol/kg was significantly smaller than that of the controls, and no side effects were observed in the 1α(OH)D 3 ‐treated mice. Marked tumor chondrogenesis was observed in human osteosarcoma treated with 1α(OH)D 3 in athymic mice. The combination of 1α,25(OH) 2 D 3 at 10 −8 M and CDDP at 2 μg/ml significantly enhanced both the differentiation and the growth inhibition in vitro. Our study apparently is the first demonstration that vitamin D 3 metabolites have an antitumor and differentiating effect on human osteosarcoma cells in vitro and in athymic mice. Vitamin D 3 should be examined further to discover whether it could be a useful drug in hormonal treatment for human osteosarcomas.