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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張大釗(Ta-Chau Chang) | |
| dc.contributor.author | Ying-Ting Chen | en |
| dc.contributor.author | 陳瑛婷 | zh_TW |
| dc.date.accessioned | 2021-06-16T05:12:53Z | - |
| dc.date.available | 2017-08-26 | |
| dc.date.copyright | 2014-08-26 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-08-18 | |
| dc.identifier.citation | 1. (2011) 行政院衛生署台灣地區主要死因歷年統計結果.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/56008 | - |
| dc.description.abstract | 近年來本實驗室合成出一系列螢光小分子BMVC及其衍生物，可以經由螢光強度有效區別癌細胞與正常細胞的分子，同時能夠穩定DNA四股結構，進而能選擇性毒殺癌症細胞。其中之一的BMVC-12C-P有機會可以發展成抗癌藥物的分子，該分子在BMVC九端的氮上接12個碳鏈與methyl-Piperidinium iodide，進入癌細胞後主要會聚集在粒線體，但在正常細胞中只有少量分佈在粒線體，另外發現其累積於粒線體的量與細胞毒殺性成正比的關係，因此BMVC-12C-P可以選擇性的殺死癌細胞。根據先前系列的研究，我們推測BMVC-12C-P會作用在mtDNA，特別是基因中G-rich的序列。
而在本篇論文中，我們透過研究結構類似的分子，觀察其在細胞內的作用模式，希望能對我們先前所提出BMVC-12C-P毒殺癌細胞的假說進行驗證。從實驗室先前的研究觀察到o-BMVC進細胞後與BMVC-12C-P同樣位在粒線體，但卻無法對細胞造成毒殺，因此我們從此處著手，第一部分為探討不同碳鏈長度的o-BMVC衍生物分子對於細胞的影響，實驗結果發現o-BMVC系列分子在細胞中大部分會位在粒線體，短碳鏈(六個碳以下)的分子在細胞內的螢光強度為弱，對細胞沒有毒殺效果，而長碳鏈(八個碳以上)反之。而第二部分則是研究BMVC-12C-P與o-BMVC-12C-P兩個不同core的分子對細胞的影響，發現到此兩個分子對細胞的影響十分類似，o-BMVC-12C-P同樣位於癌細胞內粒線體比例較高、且對癌細胞有較強的毒殺效果，另外，o-BMVC-12C-P同樣會破壞粒線體膜電位，且抑制mtND3基因(內含G-rich序列)的表現，在in vitro的實驗中發現此兩個分子對DNA結構會具有選擇的結合，較容易作用在G四股結構，且o-BMVC-12C-P對於mtND3-2的G四股結構穩定效果較BMVC-12C-P好。 從第一部分的實驗結果我們推測短碳鏈分子沒有與mtDNA作用，因此螢光較弱也無毒殺性，長碳鏈分子反之，由此可合理說明之前BMVC-12C-P毒殺細胞是透過與mtDNA作用的假說。且從第二部分可以發現到o-BMVC-12C-P與BMVC-12C-P毒殺細胞的機制類似。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2021-06-16T05:12:53Z (GMT). No. of bitstreams: 1 ntu-103-R01223205-1.pdf: 6257126 bytes, checksum: d071289aedd7903c74474c9fa0b2c2d4 (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | 誌謝…………………...……………………………………………………………….ii
摘要…..…...…………………………………………………………………………..iv Abstract…....…...……………………………………………………………………..vi 目錄………………………………………………………………………………….viii 圖目錄………………………………………………………………………………....x 表目錄………………………………………………………………………………..xii 第一章 緒論 1 1.1 癌症 1 1.2 粒線體 2 1.3 BMVC及其衍生物 4 第二章 研究目的 12 第三章 實驗材料與方法 13 3.1 細胞培養 13 3.3 BMVC衍生物於細胞內影像集位置觀察 14 3.4 定量分析細胞內BMVC衍生物的螢光強度 15 3.5 細胞存活率分析(MTT assay) 16 3.6 細胞群落形成分析(Colony formation assay) 17 3.7 粒線體模電位分析 17 3.8 逆轉錄聚合酶鏈式反應(Reverse Transcription-Polymerase Chain Reaction，RT-PCR) 18 3.9 抽取total DNA 19 3.10 聚合酶連鎖反應(Polymerase chain reaction，PCR) 19 3.11 洋菜膠體電用分析(Agarose electrophoresis) 20 3.12 圓二色旋光光譜儀 20 3.13 聚丙烯醯胺電泳(PAGE) 20 第四章 結果 22 4.1 探討o-BMVC九端碳鏈長度的改變對細胞的表現影響 22 4.1.1 o-BMBV衍生物吸收螢光光譜 22 4.1.2 o-BMVC衍生物在細胞內螢光強度 24 4.1.3 o-BMVC衍生物進入細胞後所位於的胞器 26 4.1.4 o-BMVC衍生物對細胞毒殺性 30 4.2 探討相同碳鏈長不同core的BMVC-12C-P及o-BMVC-12C-P小分子對細胞的影響 34 4.2.1 BMVC-12C-P與o-BMVC-12C-P在不同株細胞內的螢光表現量比較 34 4.2.2 BMVC-12C-P與o-BMVC-12C-P在不同株細胞存在於粒線體中的比例 36 4.2.3 o-BMVC-12C-P與BMVC-12C-P對於細胞毒殺性比較 38 4.2.4 粒線體膜電位測試 41 4.2.5 o-BMVC-12C-P抑制粒線體內基因表現 43 4.2.6 o-BMVC-12C-P與BMVC-12C-P對於mtND3可能形成G四股結構序列穩定度比較 46 4.2.7 G四股結構穩定劑o-BMVC-12C-P與BMVC-12C-P對雙股DNA及G四股結構DNA親合力比較 50 第五章 討論 52 第六章 結論 58 參考資料 59 | |
| dc.language.iso | zh-TW | |
| dc.subject | 化學結構 | zh_TW |
| dc.subject | G四股結構DNA | zh_TW |
| dc.subject | 粒線體 | zh_TW |
| dc.subject | 螢光小分子 | zh_TW |
| dc.subject | 癌細胞選擇性 | zh_TW |
| dc.subject | fluorescent small molecule | en |
| dc.subject | G-quadruplex DNA | en |
| dc.subject | Mitochondria | en |
| dc.subject | chemical sturcture | en |
| dc.subject | cancer cell selectivity | en |
| dc.title | 探討螢光o-BMVC衍生物破壞粒線體與癌細胞的作用機制 | zh_TW |
| dc.title | Investigation of Fluorescent o-BMVC Derivatives for Mitochondrial Dysfunction and Cancer Research | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林敬哲,陳進庭,牟中原 | |
| dc.subject.keyword | 粒線體,G四股結構DNA,螢光小分子,癌細胞選擇性,化學結構, | zh_TW |
| dc.subject.keyword | Mitochondria,G-quadruplex DNA,fluorescent small molecule,cancer cell selectivity,chemical sturcture, | en |
| dc.relation.page | 62 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2014-08-18 | |
| dc.contributor.author-college | 理學院 | zh_TW |
| dc.contributor.author-dept | 化學研究所 | zh_TW |
| 顯示於系所單位： | 化學系 | |
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