Antitumor activity of vitamin A and its derivatives.
Antitumor activity of vitamin A and its derivatives.
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维生素A及其衍生物的抗肿瘤活性。
DOI：
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发表时间：
1984
期刊：
影响因子：
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通讯作者：
H. Moriwaki
中科院分区：
文献类型：
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作者：
Yasutoshi Muto;H. Moriwaki
研究了维生素a类化合物对实验性皮肤和肝脏肿瘤发展的抑制作用，特别关注了聚戊酸3,7,11,15-四甲基-2,4,6,10,14-十六进五烯酸（E-5166）的新合成衍生物。饮食中维生素A含量对化学诱导小鼠皮肤乳头状瘤的发生率有显著影响。当口服200 mg/kg体重时，β -胡萝卜素在一定程度上缓解了皮肤乳头瘤（14天-16%），但其效果远弱于E-5166（-43%）。E-5166还能显著降低化学致癌物诱导的实验性肝癌大鼠以及基因决定的“自发性”肝癌小鼠（C3H/HeNCrj）的肿瘤发生率。进一步的化学研究表明，在肝癌中局部缺乏视黄醇，而在邻近的正常肝脏中则没有。特别是，在自发性肝癌小鼠的肿瘤中新检测到无氢视黄醇，这表明视黄醇向无活性代谢物的转化增加。此外，细胞类维甲酸结合蛋白f型（一种癌胎蛋白）也新出现在肝癌组织中，这表明E-5166对肝癌发生的预防作用至少部分是通过其与新的类维甲酸受体结合介导的。
Studies were conducted for investigation of the inhibitory effect on the development of experimental tumors of the skin and liver with vitamin A-like compounds, with a particular focus on a new synthetic derivative of the polyprenoic acid 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (E-5166). Incidence of skin papilloma, chemically induced in mice, was significantly influenced by dietary vitamin A contents. When given orally at a dose of 200 mg/kg body weight, beta-carotene regressed the skin papilloma to some extent (-16% at 14 days), although its effect was much weaker than that of E-5166 (-43%). E-5166 also significantly reduced tumor incidences of experimental hepatomas induced by chemical carcinogen in rats as well as in "spontaneous" hepatoma-bearing mice (C3H/HeNCrj) genetically determined. Further chemical studies revealed that retinol was locally deficient in the hepatomas but not in adjacent normal livers: In particular, anhydroretinol was newly detected in the tumors of spontaneous hepatoma-bearing mice, suggesting increased conversion of retinol into the inactive metabolite. Moreover, cellular retinoid-binding protein, F-type (an oncofetal protein), also newly appeared exclusively in the hepatoma tissues, suggesting that the preventive effect of E-5166 on hepatocarcinogenesis was mediated, at least in part, through its binding with the new retinoid receptor.