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.