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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 黃德富 | |
dc.contributor.author | Chih-Yuan Tan | en |
dc.contributor.author | 譚智元 | zh_TW |
dc.date.accessioned | 2021-06-13T01:43:37Z | - |
dc.date.available | 2016-10-07 | |
dc.date.copyright | 2011-10-07 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-02 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/30207 | - |
dc.description.abstract | Angiogenesis is a multistep process of new blood vessel formation from preexisting vasculature, which is essential in many pathological disorders. Endothelial cells play a critical role in the processes of angiogenesis including cell proliferation, migration, differentiation and tube formation. Anti-angiogenesis is a therapeutic strategy for certain cancers. In the present study, we found Than42, 5-(4-Hydroxy-3-methoxyphenyl)-3-(5-methyl-2-furyl)-1-phenylpyrazole inhibited human umbilical vein endothelial cells (HUVECs) growth under vascular endothelial growth factor (VEGF) stimulation by MTT asssay. Than42 preferentially inhibited the adhesion of HUVECs to fibrinogen by affecting B3 integrin affinity/expression. In addition, Than42 inhibited VEGF-induced tube formation and cell migration in vitro in a concentration-dependent manner. By using Annexin V/PI double staining, we found Than42 inhibited cell growth by inducing apoptosis. Than42 also concentration-dependently blocked VEGF-induced reactive oxygen species (ROS) production. In regard to intracellular signal transduction, Than42 blocked the activation of PI3K/AKT, ERK1/2, Rac1/Cdc42, endothelial NO synthase (eNOS) and the nuclear translocation of NF-kB stimulated by VEGF. VEGF-induced matrix metalloproteinase (MMP)-2 protein and mRNA expression were also decreased by the treatment of Than42. In addition, VEGF-induced FAK phosphorylation and actin cytoskeleton reorganization in HUVECs were affected by Than42. Under hypoxia condition, Than42 also concentration-dependently interfered with the activation of HIF-1d and Akt. Besides, Than42 inhibited VEGF-induced angiogenesis in Matrigel plug implantation assay in vivo. These results indicate that Than42 exhibits anti-angiogenic activity both in vivo and in vitro through the blockade of NF-kB and VEGF-VEGFR-2 signaling pathways, suggesting that Than42 could be a potential compound as an anti-angiogenic agent. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T01:43:37Z (GMT). No. of bitstreams: 1 ntu-100-R98443007-1.pdf: 14796442 bytes, checksum: 9c5bbc836bf49cd6a25155ee102c51a8 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 中文摘要 i
Abstract iii Abbreviation table v Chapter 1 Introduction 1 1.1 Angiogenesis 1 1.2 Tumor angiogenesis 2 1.3 Vascular endothelial growth factor (VEGF) 3 1.4 Vascular endothelial growth factor receptor(VEGFR) 5 1.5 VEGF-induced signal transduction 5 1.6 NF-kB 7 1.7 Hypoxia and hypoxia inducible factor-1 (HIF-1) 9 1.8 Reactive oxygen species (ROS) and Rac1 10 1.9 Than42 11 Chapter 2 Materials and methods 30 2.1 Materials 30 2.2 Cell culture 31 2.3 Cell viability assay 32 2.3.1 Cell viability assay- Serum-induced cell growth 32 2.3.2 Cell viability assay- VEGF-induced cell growth 32 2.4 Adhesion assay. 33 2.5 Flow cytometric analysis for integrin binding assays 33 2.6 In vitro tube formation assay 34 2.7 Migration assay. 35 2.8 RNA preparation and RT-PCR. 35 2.9 Immunofluorescence microscopy. 36 2.10 Analysis of cell apoptosis by Annexin V/PI double staining . 37 2.11 Immunoblot analysis 38 2.12 Electrophoretic mobility shift assay (EMSA). 38 2.13 Assay of Intracellular Reactive Oxygen Species 39 2.14 Hypoxic growth conditions and treatment 40 2.15 Matrigel plug angiogenesis assay 40 2.16 Statistical analysis 41 Chapter 3 Results 42 3.1 Effect of Than42 on endothelial cell growth 42 3.2 Effect of Than42 on HUVEC adhesion to immobilized ECMs 42 3.3 Than42 inhibited VEGF-induced tube formation in vitro 43 3.4 Effect of Than42 on VEGF-induced endothelial cells migration 44 3.5 Than42 inhibits VEGF-induced MMP-2 protein and mRNA levels 44 3.6 Effect of Than42 on the small GTPases of the Rho family 45 3.7 Than42 inhibited phosphorylation of FAK and organization of the actin cytoskeleton 45 3.8 Than42 caused endothelial cell apoptosis. 46 3.9 Than42 inhibited the survival of endothelial cells through the VEGF-induced PI3K/Akt and ERK pathway 48 3.10 Than42 inhibited VEGF-induced phosphorylation of eNOS 48 3.11 Than42 suppressed the NF-kB translocation into the nucleus 49 3.12 Than42 inhibited VEGF-induced ROS production in HUVECs 50 3.13 Than42 inhibited hypoxia-induced activation of HIF-1α and Akt 50 3.14 Effect of Than42 on VEGF induced angiogenesis in Matrigel plug assay 51 Chapter 4 Discussion 82 Chapter 5 Conclusion and Perspectives 90 References 94 | |
dc.language.iso | en | |
dc.title | Than42抑制血管內皮生長因子引發之血管新生作用機轉之研究 | zh_TW |
dc.title | Than42 inhibits angiogenesis induced by vascular endothelial growth factor and its mechanism of action | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 鄧哲明,顏茂雄,楊春茂,吳文彬 | |
dc.subject.keyword | 血管新生,血管內皮生長因子,人類臍靜脈內皮細胞, | zh_TW |
dc.subject.keyword | Angiogenesis,VEGF,HUVEC, | en |
dc.relation.page | 110 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-08-02 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥理學研究所 | zh_TW |
顯示於系所單位: | 藥理學科所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
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ntu-100-1.pdf 目前未授權公開取用 | 14.45 MB | Adobe PDF |
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