Thioacetamide accelerates steatohepatitis, cirrhosis and HCC by expressing HCV core protein in transgenic zebrafish Danio rerio.
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.
Rekha
Ravikumar Deepa
RD
Laboratory of Marine Molecular Biology and Biotechnology, Institute of Cellular and Organismic Biology, Academia Sinica, NanKang, Taipei 11529, Taiwan.
Amali
Aseervatham Anusha
AA
Her
Gour Mour
GM
Yeh
Yang Hui
YH
Gong
Hong-Yi
HY
Hu
Shao-Yang
SY
Lin
Gen-Hwa
GH
Wu
Jen-Leih
JL
D000818:Animals; D030801:Animals, Genetically Modified; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000235:genetics / Q000821:virology; D056486:Chemical and Drug Induced Liver Injury; D017931:DNA Primers; D005234:Fatty Liver / Q000139:chemically induced / Q000235:genetics / Q000821:virology; D016174:Hepacivirus / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics / Q000821:virology; D008107:Liver Diseases / Q000235:genetics / Q000821:virology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000821:virology; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013853:Thioacetamide / Q000633:toxicity*; D014758:Viral Core Proteins / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics*
D017931:DNA Primers; D014758:Viral Core Proteins; D013853:Thioacetamide