Oral administration of 1 alpha hydroxyvitamin D3 inhibits tumor growth andmetastasis 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 mod el. A solution of 1-D3 oi vehicle alone was administered daily for 2 weeks to tumor-bearing mice using an esophageal tribe and tumor size was serially monitored In 1-D3-treated mice, the growth of Dunn osteosarcoma was signif icantly suppressed ill a dose-dependent manner. Histologically, tumor cells in the control mice proliferated in marginal legions of rite tumor with wi de central necrosis, whereas in the 1-D3-treated mice, tumor cells were dis tributed as scattered islands among extensive necrotic tissue. The mean tum or necrosis nr en 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 cytofluoro metric cell cycle distribution ol the histological mitotic index between co ntrol and 1-D3-treated tumors. When 1-D3 was administered to mice from 2 da ys before to 2 weeks after transplantation of the tumor, there were signifi cantly fewer metastatic foci in the lungs in 1-D3-treated mice than ill con trol mice. We also tested the effect of coadministration of 1-D3 and doxoru bicin on the growth of Dunn osteosarcoma and found that these two drugs act additively to suppress tumor growth. These results indicated that 1-D3 giv en 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.