Ishizaki Sonoko, Nishiyama Megumi, Hagiwara Asami
Exploratory Research Laboratories, Research Center, Ajinomoto Pharmaceuticals Co., Ltd., Kawasaki, Japan.
J Clin Exp Hepatol. 2013 Sep;3(3):192-7. doi: 10.1016/j.jceh.2013.08.008. Epub 2013 Sep 6.
Obesity increases the risk of fatty liver disease and liver cancer. There are several models of obesity-associated hepatocellular carcinoma, but tumor development in these models is slow.
We investigated Zucker fatty rats, a model of obesity and insulin resistance, to discover if diethylnitrosamine (DEN), a potent liver carcinogen, might enhance liver carcinogenesis. We also investigated the effect of branched chain amino acids (BCAA) against the development of liver cancer.
Incidence and number of hepatocellular carcinomas and adenomas were significantly greater in DEN-treated Zucker fatty rats than in DEN-treated lean rats. All treated Zucker fatty rats developed hepatocellular carcinoma within 16 weeks. Long-term BCAA supplementation significantly reduced expression of CyclinD1, PCNA, thymidine kinase, Bcl-2, and GST-p and increased expression of p21 in the liver. Furthermore, BCAA treatment significantly reduced the area of GST-p positive foci.
Long-term BCAA treatment may induces cell cycle arrest and apoptotic induction, thus suppressing pre-neoplastic lesions.
肥胖会增加脂肪肝疾病和肝癌的风险。有几种肥胖相关肝细胞癌模型，但这些模型中的肿瘤发展缓慢。
我们研究了Zucker肥胖大鼠，一种肥胖和胰岛素抵抗模型，以探究强效肝脏致癌物二乙基亚硝胺（DEN）是否可能增强肝癌发生。我们还研究了支链氨基酸（BCAA）对肝癌发展的影响。
经DEN处理的Zucker肥胖大鼠的肝细胞癌和腺瘤的发生率及数量显著高于经DEN处理的瘦大鼠。所有经处理的Zucker肥胖大鼠在16周内都发生了肝细胞癌。长期补充BCAA可显著降低肝脏中细胞周期蛋白D1、增殖细胞核抗原、胸苷激酶、Bcl-2和谷胱甘肽S-转移酶p（GST-p）的表达，并增加p21的表达。此外，BCAA处理显著减少了GST-p阳性灶的面积。
长期BCAA治疗可能诱导细胞周期停滞和凋亡诱导，从而抑制癌前病变。
