Generation of a Zebrafish Model for Anti-Intrahepatic Cholangiocarcinoma Drug Screening

• Main Authors: Teng, Wei-Lin, 滕暐林
• Other Authors: Wu, Jen-Leih
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/23208518555809201768

碩士 === 國立臺灣海洋大學 === 生命科學暨生物科技學系 === 103 === Intrahepatic cholangiocarcinoma (ICC) is the second most common type of primary liver cancer. It is a rare malignant tumor that not easy to detect at early stage. Today, there is no effective adjuvant treatment for ICC. Therefore, to establish a platform for drug screening is extremely important. To develop high throughput drug screening platform for anti-ICC drug screening, we developed a xenograft model by transplant fluorescent-labeled human bile duct cancer cells into the yolk sac of 2-day-old zebrafish embryos. The established ICC model of HBx+HCP transgenic zebrafish was used to evaluate candidate drugs. According to the results of pathway maps of zebrafish ICC, Sorafenib (Nexavar), XAV-939, LY2109761 and SB431542 were used to test their anti-ICC ability in ICC cells, xenografts and HBx+HCP transgenic zebrafish, respectively. In the analysis of cell cycle, results revealed significant cell population in sub G1 area when cells were treated with Sorafenib, XAV-939, LY2109761, and SB431542, respectively. In migration assay, the results showed that LY2109761 and SB431542 reduced the ICC cells migration ability; they also inhibited TGF1 pathway downstream gene and metastasis marker mmp9 and mmp2 gene expression. In ICC xenografts, dissemination rate were also reduced by LY2109761 and SB431542 treatment. Compare the results above shows LY2109761 is the more effective drug than others. In the inhibition of ICC in HBx and HCP transgenic zebrafish, LY2109761 inhibited 86% ICC formation compared with control. Taken together, this data demonstrates the potential of LY2109761 to inhibit ICC formation.