Rekha Ravikumar Deepa, Amali Aseervatham Anusha, Her Gour Mour, Yeh Yang Hui, Gong Hong-Yi, Hu Shao-Yang, Lin Gen-Hwa, Wu Jen-Leih
Laboratory of Marine Molecular Biology and Biotechnology, Institute of Cellular and Organismic Biology, Academia Sinica, NanKang, Taipei 11529, Taiwan.
Toxicology. 2008 Jan 14;243(1-2):11-22. doi: 10.1016/j.tox.2007.09.007. Epub 2007 Sep 14.
Hepatocellular carcinoma (HCC) is one of the common cancers worldwide, caused by Hepatitis C virus (HCV) and hepatotoxins. Here we report the development of HCC in wild type as well as HCV core protein (HCP)-transgenic zebrafish upon treatment with a hepatotoxin, thioacetamide (TAA). Two-fold accelerated HCC development could be achieved in the TAA-treated transgenic fish, that is, the progression of the disease in TAA-treated wild type zebrafish developed HCC in 12 weeks whereas that of HCP-transgenic zebrafish shortened the HCC progression to 6 weeks. Histopathological observation showed the specific pathological features of HCC. The HCC progression was confirmed through RT-PCR that revealed an up and down regulation of different marker genes at various stages of HCC progression such as, steatohepatitis, fibrosis and HCC. Moreover, HCV core protein expressed in the HCP-transgenic zebrafish and TAA synergistically accelerate the HCC development. It must be mentioned that, this is the first report revealing HCV core protein along with TAA to induce HCC in zebrafish, particularly, in a short period of time comparing to mice model. As zebrafish has already been considered as a good human disease model and in this context, this HCC-zebrafish model may serve as a powerful preclinical platform to study the molecular events in hepatocarcinogenesis, therapeutic strategies and for evaluating chemoprevention strategies in HCC.
肝细胞癌（HCC）是全球常见的癌症之一，由丙型肝炎病毒（HCV）和肝毒素引起。在此，我们报告了野生型以及HCV核心蛋白（HCP）转基因斑马鱼在用肝毒素硫代乙酰胺（TAA）处理后发生HCC的情况。在用TAA处理的转基因鱼中，HCC的发展速度加快了两倍，也就是说，在用TAA处理的野生型斑马鱼中，疾病进展到12周时发展为HCC，而HCP转基因斑马鱼的HCC进展缩短至6周。组织病理学观察显示了HCC的特定病理特征。通过RT-PCR证实了HCC的进展，该检测揭示了在HCC进展的各个阶段，如脂肪性肝炎、纤维化和HCC中，不同标记基因的上调和下调。此外，HCP转基因斑马鱼中表达的HCV核心蛋白与TAA协同加速了HCC的发展。必须提到的是，这是第一份揭示HCV核心蛋白与TAA一起在斑马鱼中诱导HCC的报告，特别是与小鼠模型相比，在短时间内即可诱导。由于斑马鱼已被视为一种良好的人类疾病模型，在此背景下，这种HCC斑马鱼模型可作为一个强大的临床前平台，用于研究肝癌发生的分子事件、治疗策略以及评估HCC的化学预防策略。
