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

本文研究了经肝细胞转化为活性形式的维生素D_3[1α，25(OH)_2D_3]、22-Oxa-1α，25(OH)_2D_3和1α，25(OH)_2D_3对接种小鼠肾细胞癌的BALB/c小鼠的抗肿瘤作用。给接种肿瘤的小鼠ip。2.5nmol/kg和5.0nmol/kg维生素D_3类似物，自肿瘤接种后第1天起每2天注射一次。与对照组相比，在第14天和第21天，这些类似物以剂量依赖的方式显著抑制了RencA的生长。22-氧杂-1，25(OH)_2D_3仅在5.0nmol/kg剂量时毒性作用最小。而1α(OH)D_3和1α，25(OH)_2D_3则使小鼠体重下降。用1a(OH)D_3和22-Oxa-1α，25(OH)_2D_3治疗不能引起明显的高钙血症，也不能抵消RencA小鼠血清无机磷水平的下降。组织学检查显示，IP。在第21天，这些类似物的治疗引起肿瘤的凝固性坏死，而没有观察到出血坏死和淋巴细胞浸润。这些类似物在裸鼠体内也显示了抗肿瘤作用，但这种作用不会因抗asialo GM1的治疗而改变。用比色法定量测定肿瘤血管生成活性，这些类似物以剂量依赖的方式将其抑制到对照水平的72-85%。结果表明，1，25(OH)_2D_3、1α(OH)D_3和22-氧杂-1，25(OH)_2 D_3对肾癌有潜在的治疗作用。这些类似物也有很强的抗血管生成作用。宿主免疫反应介导的T细胞和NK细胞在维生素D3类似物的抗肿瘤作用中没有任何作用。

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.