Oral administration of 1 alpha hydroxyvitamin D3 inhibits tumor growth and metastasis of a murine osteosarcoma model.
We studied the effect of oral administration of 1 alpha hydroxyvitamin D3 (1-D3) on the growth and metastatic ability of Dunn murine osteosarcoma model. A solution of 1-D3 or vehicle alone was administered daily for 2 weeks to tumor-bearing mice using an esophageal tube and tumor size was serially monitored. In 1-D3-treated mice, the growth of Dunn osteosarcoma was significantly suppressed in a dose-dependent manner. Histologically, tumor cells in the control mice proliferated in marginal regions of the tumor with wide central necrosis, whereas in the 1-D3-treated mice, tumor cells were distributed as scattered islands among extensive necrotic tissue. The mean tumor necrosis area was 55.7% in the control tumors and 94.6% in 1-D3-treated tumors (p < 0.001). There were no substantial differences in the cytofluorometric cell cycle distribution or the histological mitotic index between control and 1-D3-treated tumors. When 1-D3 was administered to mice from 2 days before to 2 weeks after transplantation of the tumor, there were significantly fewer metastatic foci in the lungs in 1-D3-treated mice than in control mice. We also tested the effect of coadministration of 1-D3 and doxorubicin on the growth of Dunn osteosarcoma and found that these two drugs act additively to suppress tumor growth. These results indicated that 1-D3 given orally inhibits tumor growth and metastases in a Dunn osteosarcoma model. Although the mechanism remains unknown, oral administration of 1-D3 might be promising as a new method of treating human osteosarcoma.
Hara
K
K
Department of Orthopaedic Surgery, Kyoto Prefectural University of Medicine, Kyoto 602, Japan.
Kusuzaki
K
K
Takeshita
H
H
Kuzuhara
A
A
Tsuji
Y
Y
Ashihara
T
T
Hirasawa
Y
Y
D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000473:pathology / Q000517:prevention & control*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin / Q000627:therapeutic use; D006887:Hydroxycholecalciferols / Q000008:administration & dosage* / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D051379:Mice; D008809:Mice, Inbred C3H; D012516:Osteosarcoma / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D006887:Hydroxycholecalciferols; D004317:Doxorubicin; C008088:alfacalcidol