Prevention of rat hepatocarcinogenesis by acyclic retinoid is accompanied by reduction in emergence of both TGF-a-expressing oval-like cells and activated hepatic stellate cells
Prevention of rat hepatocarcinogenesis by acyclic retinoid is accompanied by reduction in emergence of both TGF-a-expressing oval-like cells and activated hepatic stellate cells
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DOI：
10.1207/s15327914nc5102_10
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发表时间：
2005-01-01
影响因子：
2.9
通讯作者：
Tanaka, T
中科院分区：
文献类型：
--
作者：
Sano, T;Kagawa, M;Tanaka, T
我们研究了合成的去环维A酸类化合物NIK-333对3‘-甲基-4-二甲氨基偶氮苯(3’-MeDAB)处理的F344雄性大鼠肝癌发生的早期和晚期事件的预防作用。NIK-333连续给药10、40、80 mg/kg体重，每日1次，同时补充含3‘-MeDAB的饲料，共16wk。在实验开始后4wk和16wk处死每组动物，以确定Nik-333对癌变的早期和晚期的影响。NIK-333早期抑制肝细胞癌前体细胞转化生长因子-α表达的卵圆形细胞和肝脏主要基质生成细胞激活的肝星状细胞，晚期抑制肝细胞癌的发生。这些结果表明，NIK-333通过独特地抑制肝癌发生的早期事件，即卵圆形细胞的发育和纤维化的形成，是一种很有前途的肝癌化学预防药物。
We investigated the preventive effects of a synthetic acyclic retinoid, NIK-333, on the early and late events of hepatocarcinogenesis in male F344 rats treated with 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). NIK-333 was administered once a day on consecutive days at a dose of 10, 40, or 80 mg/kg body weight along with the supplementation with 3'-MeDAB-containing diet for 16 wk. Animals from each group were sacrificed at 4 and 16 wk after the commencement of the experiment to determine the effect of NIK-333 on the early and late stages of carcinogenesis, respectively. NIK-333 suppressed the emergence of both oval-like cells expressing transforming growth factor (TGF)-a, putative progenitors of hepatocellular carcinoma (HCC), and activated hepatic stellate cells, major matrix-producing cells of the liver in the early stage and inhibited the incidence of HCC in the late phase. These results suggest that NIK-333 is a promising drug for the chemoprevention of HCC by uniquely suppressing the early events of hepatocarcinogenesis, that is, development of both oval-like cells and fibrogenesis.