TUMOR REGRESSION CAUSED BY ACTIVATED VITAMIN D_3 IN MURINE RENAL CARCINOMA.

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The effect of anti-tumoral therapy using 1alpha-hydroxvitamin D_3 [1alpha (OH) D_3] which is converted by liver cells to active from of vitamin D_3 [1alpha, 25 (OH) _2D_3], 22-Oxa-1alpha, 25 (OH) _2 D_3 and 1alpha, 25 (OH) _2D_3 WAS inveatigated in BALB/c mice inoculated with murine renal cell carcinoma (Renca). Tumor-inoculated mice were given i.p. 2.5 nmol/kg and 5.0 nmol/kg of these vitamin D_3 analogues every 2 days from Day 1 after tumor inoculation. Treatment with these analogues significantly suppressed the growth of Renca in a dose-dependent manner compared with control mice on Days 14 and 21. Toxic effect of 22-oxa-1,25 (OH) _2D_3 was only minimally by dosed of 5.0 nmol/kg. However 1alpha (OH) D_3 and 1alpha, 25 (OH) _2D_3 caused a decrease in body weight of the mice. Treatment with 1a (OH) D_3 and 22-Oxa-1alpha, 25 (OH) _2D_3 caused no appreciated hypercalcemia and did not counteract the decrese of serum inorganic phosphorus level in mice bearing Renca. Histological examination showed that i.p. treatment of these analogues caused coagulative necrosis of the tumors on Day 21, while hemorrhargic necrosis and lymphocyte infiltration were not observed. The antitumoral effect of these analogues was also demonstrated in athymic nude mice and it did not altered by treatment with anti-asialo GM1. Tumor angiogenic activity was measured quantitatively using a colorimetric assay and it was inhibited to 72-85% of the control level in a dose-dependent manner by these analogues. Microangiography showed a lower density of angiogenesis and thinner novessels than control tumors.From these results, it was concluded that 1,25 (OH) _2D_3,1alpha (OH) D_3 and 22-oxa-1,25 (OH) _2 D_3 were potensially effective for renal cell carcinoma. The potent antiangiogenic action of these analogues was also demonstrated. Host immune response mediated T cells and NK cells did not any role in antitumoral effect of these vitamin D_3 analogues.