To investigate the role of monoamine oxidase A (MAO-A) in colorectal cancer
| Autor: | Chin-Han Huang, 黃勁翰 |
|---|---|
| Rok vydání: | 2014 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 102 Monoamine oxidase A (MAO-A), a catecholamine neurotransmitter degrading enzyme located in mitochondria outer membrane, is well-known for its role in psychiatric and neurological disorder. Monoamine oxidase inhibitors are also proved to be an effective treatment for depression and Parkinson’s disease. Recently, MAO-A was reported as a biomarker in several cancers. Therefore, MAO-A may act as a novel therapy target or a predictor of clinical outcomes. However, the role of MAO-A in cancer initiation and progression is still not comprehensive understood. The aim of this study is to investigate the role of MAO-A in colorectal cancer tumorigensis. Firstly, we used MAO-A inhibitor clorgyline and established the MAO-A stable knockdown mice colorectal cancer cell lines (CT-26 shMAO-A) to study the role of MAO-A in colorectal cancer tumorigensis in vitro and in vivo. At the same time, we evaluated the expression level of MAO-A in 18 independent CRC pairs of tumor and paired normal adjacent tissues using RT-qPCR and immunohistochemistry. RT-qPCR and immunohistochemistry revealed MAO-A were highly expressed in adjacent normal tissue compared to CRC tissue. Moreover, CT-26 cells showed no difference on cell proliferation and migration whether clorgyline treatment or not. CT-26 shMAO-A cells also showed no different on proliferation and migration compared to CT-26 shGFP control cells. However, CT-26 shMAO-A #H clone cells showed significant higher invasion capability compared with CT-26 shGFP cells (p = 0.05). In animal study, some clorgyline-treated CT26-inoculated mice showed pathological lesion in liver (I: 4/13 II: 5/9 III: 3/12 (N=3), 25 – 50%). Tumor suppression ability was not significantly different in mice bearing CT-26 cells whether clorgyline treatment or not. Blood chemical of mice analysis revealed that clorgyline treatment may cause hepatotoxicity, but the occurrence of liver lesion was not correlated with hepatotoxicity. It is curiously same dosage clorgyline applied in mice bearing CT-26 shGFP cells or CT-26 shMAO-A cells, but the occurrence rate of liver lesion is relatively low (I: 0/8 II: 0/5 III: 1/5 (N=3), 0 – 20%). Liver histopathological observation showed a wide range of necrosis and infiltration of inflammatory lymphocyte in liver lesion tissue compared to PBS-treated mice. In addition, Mice with clorgyline treatment observed obvious Ductular reaction in liver. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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