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Title: Study Liver Tumorigenesis in Transgenic Tumor Zebrafish using chemical screens
Authors: ZHOU LI
Keywords: liver tumorigenesis, chemical screens, transgenic zebrafish, HCC signalling pathway
Issue Date: 1-Dec-2011
Citation: ZHOU LI (2011-12-01). Study Liver Tumorigenesis in Transgenic Tumor Zebrafish using chemical screens. ScholarBank@NUS Repository.
Abstract: Hepatocellular carcinoma (HCC) is one of the leading cancers in the world and this disease is often diagnosed at an advanced stage when potentially curative therapies are not feasible. Understanding of the molecular mechanism of HCC is vital to develop therapeutical approaches to cure this disease. In recent years, the zebrafish has become a popular model to study human diseases, particularly for small molecule screening in drug discovery. In the current study, we employed two zebrafish tumor models previously established in our lab, TO(Myc) and TO(kras) transgenic line, which contain Myc and krasv12 oncogenes respectively in a tetracycline-inducible (tet-on) system and produced HCC by doxycycline induction. To develop a rapid assay for potential anticancer drug screening, several chemical inhibitors which target a few signaling pathways involved in HCC, including MAPK pathway, JAK/STAT pathway, PI3K pathway and Myc transcription factor, were selected to treat larvae of the two transgenic lines. Following the treatment, liver images were taken and analyzed by ImageJ for two-dimensional area quantification followed by cell proliferation analysis to further investigate the inhibition effect. We observed that some inhibitors such as Stat5In and PD0325901 inhibited liver overgrowth in both TO(Myc) and TO(kras) larvae; U0126 was only effective in TO(kras) larvae but not in TO(Myc) larvae; LY294002 was able to reduce liver enlargement in TO(Myc) larvae but failed to do so in TO(kras) larvae. We conclude that inhibition of JAK/STAT pathway or MAPK pathway in both Myc and kras mediated oncogenesis suppresses tumor growth, and targeting PI3K pathway using LY294002 is a potential means to treat Myc driven oncogenesis
Appears in Collections:Master's Theses (Open)

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