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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 梁博煌(Po-Huang Liang) | |
dc.contributor.author | You-Wei Tsai | en |
dc.contributor.author | 蔡有緯 | zh_TW |
dc.date.accessioned | 2021-06-17T08:41:46Z | - |
dc.date.available | 2022-08-15 | |
dc.date.copyright | 2019-08-15 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-08-07 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74543 | - |
dc.description.abstract | 肺癌是致死率高且容易轉移(metastasis)到其他器官的一種癌症。研究使用的細胞株為CL1-5,為非小細胞肺癌(non-small cell lung cancer (NSCLC)),此類型的肺癌細胞為最常見的一種。根據先前研究發現,藉由I-Trp阻斷CCT-β與β-tubulin之間的交互作用可殺死癌細胞,而本研究使用的小分子-845,是NHRI合成出來的一系列殺菌化合物中經實驗篩選出最有潛力殺死CL1-5,且其結構是由之前使用電腦模擬出可逆型CCT-β與β-tubulin間交互作用之抑制劑中的基團與I-Trp之側鏈所組成。經實驗發現,845可誘導肺癌細胞發生內質網壓力(ER stress),進而促使肺癌細胞內的鈣離子釋放至細胞質並導致細胞凋亡。透過wound healing assay、transwell assay,發現845能抑制肺癌細胞遷移(migration)及侵入(invasion),且經由西方墨點法可知845能抑制EMT、AKT/β-catenin和integrin的訊息傳導路徑,進而抑制肺癌轉移。
總括而論,本研究發現此具有雙功能的抑制劑化合物-845具有對肺癌的抗腫瘤和抗轉移能力。 | zh_TW |
dc.description.abstract | Lung cancer has a high mortality rate and often metastasizes to other organs. The cell line used in the study was CL1-5, which is a non-small cell lung cancer (NSCLC). According to previous studies, cancer cells can be killed through blocking the interaction between CCT-β and β-tubulin by I-Trp. The small molecule compound-845 used in this study was screened among a series of bactericidal compounds synthesized by NHRI and is the most potential to kill CL1-5 cells. In addition, its structure is composed of a functional group which is similar to the reversible inhibitors of CCT-β: β-tubulin complex previously simulated by computer and a side chain of I-Trp. It has been found that compound-845 would induce ER stress in CL1-5 cells, which in turn leads to the release of intracellular calcium ion and apoptosis. Furthermore, analyzed by wound healing assay and transwell assay, it has been found that compound-845 would inhibit the migratory and invasive ability of CL1-5 cells. Moreover, compound-845 would inhibit EMT, AKT/β-catenin and integrin signaling pathway investigated by western blot, thereby inhibiting CL1-5 cell metastasis.
In conclusion, this study reveals that this dual-functional inhibitor compound-845 probably has anti-tumor and anti-metastasis ability against human lung cancer. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T08:41:46Z (GMT). No. of bitstreams: 1 ntu-108-R06b46019-1.pdf: 2210340 bytes, checksum: 33f98df47a26675c34a5b9b853ce6c56 (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | TABLE OF CONTENTS...i
ABSTRACT...iv ABBREVIATIONS...vi 1. INTRODUCTION...1 1.1. CCT...1 1.2. Tubulin...2 1.3. ER-stress...3 1.4. Mitochondria in apoptosis...4 1.5. Epithelial-Mesenchymal transition...4 1.6. Previous studies and present work...5 2. MATERIALS AND METHODS...8 2.1. Chemicals...8 2.2. Cell Culture...9 2.3. MTT assay...9 2.4. Flow cytometry...10 2.5. Colony formation assay...10 2.6. Co-immunoprecipitation...11 2.7. Proteasome activity assay...11 2.8. Measurement of intracellular calcium ion releasing...12 2.9. Measurement of caspase activities...13 2.10. Wound healing assay...14 2.11. Matrigel invasion assay...14 2.12. Gelatin zymography...15 2.13. Western blot...16 3. RESULTS...17 3.1. Effects of compound-845 on viability of CL1-5 cells...17 3.2. Effects of compound-845 on disrupting CCT-β: β-tubulin complex...18 3.3. Compound-845 induced ER stress in CL1-5 cells...18 3.4. Compound-845 treatment led to release of intracellular calcium ion...20 3.5. Increased expression and activities of apoptosis-associated proteins and caspases by compound-845 treatment...20 3.6. Compound-845 activated MAPKs...22 3.7. Effects of compound-845 on inhibiting migration of CL1-5 cells...22 3.8. Compound-845 inhibited invasion of CL1-5 cells...23 3.9. Compound-845 suppressed EMT regulators of CL1-5 cells...23 3.10. Inhibition of AKT/β-catenin and integrin pathway in CL1-5 cells by compound-845 treatment...24 3.11. Effects of compound-845 on activity and expression of MMPs in CL1-5 cells...26 4. DISCUSSION...27 5. REFERENCE...31 6. FIGURE...39 | |
dc.language.iso | en | |
dc.title | 一個可造成肺癌細胞CL1-5凋亡並抑制其轉移能力的雙功能抑制劑 | zh_TW |
dc.title | A dual-functional inhibitor causes apoptosis and inhibits metastasis of lung cancer cell line CL1-5 | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林源峰(Yuan-Feng Lin),李靜琪(Jinq-Chyi Li) | |
dc.subject.keyword | 肺癌,抗腫瘤,抗轉移, | zh_TW |
dc.subject.keyword | lung cancer,anti-tumor,anti-metastasis,EMT,AKT/β-catenin,integrin, | en |
dc.relation.page | 54 | |
dc.identifier.doi | 10.6342/NTU201902369 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2019-08-07 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科學研究所 | zh_TW |
顯示於系所單位: | 生化科學研究所 |
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