Optimal search of target onco-enzyme and analysis of abnormal metabolism in liver

• Main Authors: CHIEN,CHEN-YU, 簡辰宇
• Other Authors: WANG,FENG-SHENG
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/39669660096463226643

碩士 === 國立中正大學 === 化學工程研究所 === 104 === The cancerization of cells is not caused by a single reason. It involves the complex metabolism. In recent years, the therapy of cancer improves every day. Targeted therapy is a significant development for the treatment of cancer. The drug targets are like missiles, they are able to identify a specific tumor cell type or specific metabolism. First, we have to select a specific cancer cell as the goal, and utilize the drugs to attack specific cancer cell without harming normal cells. Therefore, how to find a suitable target of cancer is currently research emphasis. First, we chose the metabolic network model of human liver cells, Recon2 liver model, as our simulation model. Then, we used enumeration analysis to find out the results that each part of enzymes can be regulated. Finally, we compared our results with the Warburg effect hypothesis and the experimental data of KO(miR122a-/-mouse), Human Case1 and Human Case2. Furthermore, we carried out on an analysis, mutant flux balance analysis (MFBA), to get the distribution of normal liver cells and mutant liver cells in the steady state. Finally, we found out 16 candidates(13 enzymes + 3 exchange reactions) including EC 2.7.1.40 (Pyruvate kinase), EC 1.13.11.6 (3-hydroxyanthranilate 3,4-dioxygenase), EC 3.5.1.3 (Omega-amidase), and so on which with higher similarity to Warburg effect hypothesis and the experimental data. Some of these enzymes are consistent with previous literatures and had been mentioned that are correlated to liver cancer or other cancers. As for those enzymes, that had not been mentioned in the literatures will be able to make various combination with other genes or enzymes, and be valuable clinical trials direction as references in the future. Providing the possible target which may play a crucial factor in hepatocellular carcinoma progression.