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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳彥榮 | |
| dc.contributor.author | Yun Cheng | en |
| dc.contributor.author | 鄭筠 | zh_TW |
| dc.date.accessioned | 2021-07-11T15:35:39Z | - |
| dc.date.available | 2023-08-17 | |
| dc.date.copyright | 2018-08-17 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-08-15 | |
| dc.identifier.citation | American Cancer Society. (2017). Colorectal Cancer Facts & Figures 2017-2019. Atlanta: American Cancer Society
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79002 | - |
| dc.description.abstract | 大腸癌長期位居國人十大癌症榜首，全球發生率與死亡率也位居前三名。過去發現粒線體異常會導致癌症的產生，也發現癌幹細胞具有特殊的粒線體特徵以及代謝方式，顯示粒線體在發展癌症療法上為良好的潛力標的。PINK1 是負責調控粒線體的重要蛋白，過去在不同癌症中發現 PINK1 異常可能導致癌症產生，然而 PINK1 對大腸癌及大腸癌幹細胞的影響以及機制仍不清楚。在本研究中，發現大腸癌細胞及癌幹細胞的 PINK1表現量分別有下降及上升的現象，接著分析 PINK1 基因削弱對細胞及粒線體造成的影響，發現 PINK1 會幫助細胞生長以及對抗低度的氧化壓力，並可能參與高氧化壓力下細胞凋亡的開啟。此外，削弱 PINK1 會透過抑制呼吸作用影響細胞在氧化壓力下的生長以及粒線體膜電位的維持，以及減少癌幹細胞的數量。因此，我證明了 PINK1 在大腸癌細胞的生長以及癌幹細胞的維持中扮演重要的角色，也發現改變代謝作用或施加適當的氧化壓力可能有助於抑制大腸癌細胞的生長以及清除大腸癌幹細胞。 | zh_TW |
| dc.description.abstract | Colorectal cancer is the most common cancer in Taiwan and is the one of leading causes of cancer-related death in the world. In the past decade, many studies found that defects in mitochondria may promote carcinogenesis. Several studies also showed that the state of mitochondria and metabolism is unique in cancer stem cell, indicating the potential to develop mitochondria-based cancer therapy. Serine/threonine kinase named PTEN-induced kinase-1 (PINK1) play important role in mitochondrial homeostasis. Several studies have found that abnormal PINK1 is associated to tumorigenesis. But whether PINK1 have direct impact on colon cancer is still unknown. In this study, PINK1 was found down-regulated and up-regulated in colon cancer cell and cancer stem cell, respectively. Knocking down (KD) PINK1 in colorectal cancer cell line HT29 decreased cell proliferation and impaired resistance to low-level oxidative stress, which might result from the impaired function of mitophagy and accumulation of mitochondrial ROS. After induced low-level oxidative stress by antimycin A, the survival rates and mitochondrial membrane potential of PINK1 KD cells were lower than control cell, while KD PINK1 inhibited apoptosis at high-level oxidative stress. Furthermore, I found KD PINK1 impaired stress resistance through inhibiting respiration ability. And the cancer stem cells significantly decreased in PINK1 KD HT29. Overall, these finding reveal the important role of PINK1 in progression and maintenance of colon cancer cells and cancer stem cells. Alteration of metabolism or proper oxidative stress may facilitate inhibition of cancer progression and clearance of cancer stem cells. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:35:39Z (GMT). No. of bitstreams: 1 ntu-107-R05b22022-1.pdf: 1437576 bytes, checksum: d0ce728eb6a2862e8291645f890f1e04 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 中文摘要 i
Abstract ii 目錄 iii 第一章 背景介紹 1 1. 大腸癌 (colorectal cancer) 1 2. 癌幹細胞 (cancer stem cell) 1 2.1 癌幹細胞假說 (cancer stem cell hypothesis) 1 2.2 癌幹細胞的特性 2 2.3 癌幹細胞的標定 4 3. 粒線體 5 3.1 粒線體與癌症 5 3.2 粒線體的型態、功能以及恆定 6 3.3 粒線體與細胞的訊息路徑 7 3.4 粒線體與癌幹細胞 9 4. 磷酸酯酶與張力蛋白同源物誘導激酶1 (PTEN-induced putative kinase 1, PINK1) 10 4.1 PINK1 簡介 10 4.2 PINK1 的功能以及對粒線體的調控 10 4.3 PINK1 於癌症中扮演的雙重角色 11 4.4 PINK1 對癌幹細胞的調控 12 第二章 材料方法 14 1. 細胞培養 14 2. 建構細胞株 14 2.1. 慢病毒包裝載體 14 2.2. pLKO.1 系統 14 2.3. 慢病毒製作 14 2.4. 細胞感染及基因削弱 (knockdown) 效率檢測 15 3. RNA 抽取與反轉錄 15 4. 定量聚合酶鏈式反應 16 5. 蛋白質抽取 16 6. 西方墨點法 16 7. DNA 合成檢定 BrdU (Bromodeoxyuridine) assay 17 8. 細胞週期分析 17 9. 粒線體活性氧化物偵測 18 10. 細胞存活率分析——MTT 試驗 18 11. 細胞凋亡分析 18 12. 粒線體膜電位分析 19 13. 氧氣消耗速率測驗 19 14. 細胞球體形成實驗 20 15. 流式細胞儀 20 16. 5-Fu 抗藥性細胞群落形成實驗 20 17. 統計分析 21 第三章 結果 22 1. PINK1 於大腸癌組織與大腸癌幹細胞的表現量 22 2. PINK1 基因削弱使大腸癌細胞株 HT29 增生速率下降及細胞週期停滯 22 3. PINK1 KD造成大腸癌細胞株 HT29 粒線體自噬作用下降及活性氧化物累積 23 4. 氧化壓力會促進細胞凋亡並破壞粒線體膜電位 23 5. PINK1 KD 抑制 HT29 呼吸作用及氧化壓力下的細胞生長及粒線體膜電位 24 6. PINK1 基因削弱降低大腸癌幹細胞數量 25 第四章 總結與討論 26 第五章 附表與結果圖 30 表一 使用引子列表 30 表二 使用抗體列表 31 圖一 PINK1 於大腸癌組織與大腸癌幹細胞的表現量 33 圖二 PINK1 基因削弱使大腸癌細胞株 HT29 增生速率下降及細胞週期停滯 34 圖三 PINK1 基因削弱造成大腸癌細胞株 HT29自噬作用下降及活性氧化物累積 35 圖四 氧化壓力會促進細胞凋亡並破壞粒線體膜電位 37 圖五 PINK1 KD 抑制呼吸作用及氧化壓力下的細胞生長及粒線體膜電位 39 圖六 PINK1 基因削弱降低大腸癌幹細胞數量 40 第六章 參考資料 42 第七章 附錄 49 | |
| dc.language.iso | zh-TW | |
| dc.subject | 大腸癌 | zh_TW |
| dc.subject | 氧化壓力 | zh_TW |
| dc.subject | 癌幹細胞 | zh_TW |
| dc.subject | 粒線體自噬作用 | zh_TW |
| dc.subject | 粒線體 | zh_TW |
| dc.subject | PINK1 | zh_TW |
| dc.subject | oxidative stress | en |
| dc.subject | cancer stem cell | en |
| dc.subject | mitophagy | en |
| dc.subject | colon cancer | en |
| dc.subject | PINK1 | en |
| dc.subject | mitochondria | en |
| dc.title | PINK1 對大腸癌的調控 | zh_TW |
| dc.title | PTEN-induced kinase 1 in Regulation of Colon Cancer | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 黃楓婷,蔡素宜 | |
| dc.subject.keyword | 大腸癌,癌幹細胞,粒線體,PINK1,粒線體自噬作用,氧化壓力, | zh_TW |
| dc.subject.keyword | colon cancer,cancer stem cell,mitochondria,PINK1,mitophagy,oxidative stress, | en |
| dc.relation.page | 49 | |
| dc.identifier.doi | 10.6342/NTU201803493 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-08-15 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| dc.date.embargo-lift | 2023-08-17 | - |
| 顯示於系所單位： | 生化科技學系 | |
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