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

活性维生素 D_3 在鼠肾癌中引起的肿瘤消退。

• 批准号: 05671331
• 负责人: FUJIOKA Tomoaki
• 金额: $ 1.34万
• 依托单位: IWATE MEDICAL UNIVERSITY SCHOOL of MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671331/
• 关键词: Activated vitamin D_3; Antitumoral effercts; Tumor angiogenesis; Microangiography; Colorimetric assay; 腫瘍血管新生阻害剤; 腎癌; 1,25(OH)_2D_3; 1a(OH)D_3; 22-oxa-1a,25(OH)_2D_3; Renca

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.

本文观察了经肝细胞转化为维生素D_3 [1 α，25（OH）_2D_3]、22-Oxa-1 α，25（OH）_2D_3和1 α，25（OH）_2D_3的1 α-羟基维生素D_3 [1 α（OH）D_3]对小鼠肾癌的治疗作用。从接种肿瘤后第1天开始，每隔2天腹腔注射2.5nmol/kg和5.0nmol/kg维生素D_3类似物。在第14天和第21天，与对照小鼠相比，用这些类似物处理以剂量依赖性方式显著抑制了Renca的生长。22-oxa-1，25（OH）_2D_3仅在5.0nmol/kg剂量下有轻微毒性作用。而1 α（OH）D_3和1 α，25（OH）_2D_3则引起小鼠体重下降。1a（OH）D_3和22-Oxa-1alpha，25（OH）_2D_3对Renca荷瘤小鼠无明显的高钙血症，也不对抗血清无机磷水平的下降。组织学检查显示，这些类似物的腹膜内处理在第21天引起肿瘤的凝固性坏死，而未观察到出血性坏死和淋巴细胞浸润。这些类似物的抗肿瘤作用也在无胸腺裸鼠中得到证实，并且用抗去唾液酸GM 1治疗不会改变。使用比色测定法定量测量肿瘤血管生成活性，并且这些类似物以剂量依赖性方式将其抑制至对照水平的72-85%。结果表明，1，25（OH）_2D_3，1alpha（OH）_3，22-oxa-1，25（OH）_2D_3对肾癌有较好的治疗作用。这些类似物的有效的抗血管生成作用也被证明。宿主免疫应答介导的T细胞和NK细胞在维生素D_3类似物的抗肿瘤作用中不起作用。

项目成果

Fujioka, T.et al.: "Vitamin D_3 analogues suppressed tumor angiogenesis and inhibited growth of renal adenocarcinoma in mice." BIOTHERAPY. 8. 196-200 (1994)

Fujioka, T. 等人：“维生素 D_3 类似物可抑制小鼠肿瘤血管生成并抑制肾腺癌的生长。”

藤岡 知昭 他: "マウス腎癌におけるビタミンD_3誘導体による血管新生阻害作用と抗腫瘍効果" BIOTHERAPY. 8. 196-200 (1994)

Tomoaki Fujioka 等：“维生素 D_3 衍生物对小鼠肾癌的血管生成抑制和抗肿瘤作用”BIOTHERAPY。8. 196-200 (1994)

藤岡 知昭 他: "血管新生阻害作用TNP-470のマウス腎癌に対する抗腫瘍効果" 医学のあゆみ. 172. 671-675 (1995)

Tomoaki Fujioka 等：“血管生成抑制剂 TNP-470 对小鼠肾癌的抗肿瘤作用”，医学史 172. 671-675 (1995)。

Suzuki, Y.et al.: "Tumor angiogenesis in human renal cell carcinoma." Ann Soci BCG ・ BRM. 17. 63-66 (1994)

Suzuki, Y. 等：“人肾细胞癌中的肿瘤血管生成。”Ann Soci BCG·BRM 17. 63-66 (1994)

藤岡知昭、他: "マウス腎癌に対する活性ビタミンD_3およびコルチゾンの血管新生阻害作用" 医学のあゆみ. 166(9). 619-620 (1993)

Tomoaki Fujioka 等人：“活性维生素 D_3 和可的松对小鼠肾癌的血管生成抑制作用”，医学史 166(9) 619-620 (1993)。