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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 郭彥彬(Yen-Ping Kuo) | |
| dc.contributor.author | Yun-Jia Huang | en |
| dc.contributor.author | 黃雲佳 | zh_TW |
| dc.date.accessioned | 2022-11-25T06:33:05Z | - |
| dc.date.copyright | 2021-10-01 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-18 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/82166 | - |
| dc.description.abstract | 根據我國衛福部108年國人十大死因統計，惡性腫瘤為十大死因中的首位，而口腔癌為十大癌症發生率的第五位。在台灣，口腔癌的發生與抽菸、喝酒、嚼食檳榔有密切的關係，檳榔中所含的檳榔鹼Arecoline是造成口腔癌主要的致病因子，但其致病機轉仍未詳細闡述。文獻指出甲硫胺酸腺苷轉移酶2A (methionine adenosyltransferase 2A (MAT2A))在許多癌症中都有過度表現的情況，包括肝癌、乳癌、結腸癌等，但其在口腔癌中的相關表現及機轉均還未被探討。MAT2A可催化生物體中S-adenosylmethionine (SAM)的合成，參與甲硫胺酸循環，於生物體代謝至關重要。實驗室初步研究發現口腔癌檢體有MAT2A過度表現。 本研究中發現Arecoline會誘導口腔癌SAS及CA922細胞株中的MAT2A表現。TGF-β1中和抗體、ALK5抑制劑 (SB431542)及Smad3抑制劑(SIS3)可降低Arecoline所誘導的SAS及CA922細胞中MAT2A表現，顯示Arecoline是經由TGF-β1訊息傳遞路徑誘導口腔上皮細胞中MAT2A的表現。MAT2A siRNA抑制MAT2A表現量高的SAS細胞株的MAT2A表現，發現抑制MAT2A 會使SAS細胞轉移與侵襲性降低，並下調由TGF-β1所引起的癌幹細胞標誌(stemness marker)上升。文獻指出，癌幹細胞會參與腫瘤維持、轉移及復發，是使其對化療、放療產生抗性的原因之一，而聚球體(sphere)細胞是一種能表現較多幹細胞的特性的細胞，本研究針對SAS細胞及SAS sphere細胞進行比較，結果顯示SAS sphere細胞有較高的MAT2A表現量。通過sphere forming assay觀察MAT2A siRNA抑制的 SAS sphere細胞，可發現SAS sphere細胞形成聚球體的能力降低，且同時會下調部分癌幹細胞標誌，包括: CD133、CD44、KLF4、OCT4A和Nanog的表現。本實驗也以MAT2A抑制劑FIDAS-5處理SAS細胞，並透過transwell migration assay與invasion assay觀察，可發現其侵襲與轉移能力均降低。若是使用FIDAS-5處理SAS sphere，可發現其也可降低SAS sphere細胞形成聚球體的能力，並下調癌幹細胞標誌，包括包括: CD133、CD44、KLF4、OCT4A、SOX2和Nanog的表現，顯示FIDAS-5具有治療口腔癌的潛力。 | zh_TW |
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| dc.description.tableofcontents | 口試委員會審定書 I 謝誌 II 中文摘要 III Abstract IV 目錄 V 第一章 導論 1 1.1口腔癌 1 1.2 檳榔鹼 4 1.3 轉型生長因子Transforming growth factor-β1 (TGF-β1) 6 1.4 Methionine Adenosyltransferase 2A (MAT2A) 8 第二章、研究動機與目的 12 第三章 材料與方法 13 3.1 細胞株與細胞培養 13 3.1.1細胞株的培養 13 3.1.2繼代培養 13 3.2 藥物處理 13 3.2.1 種細胞以及starvation 13 3.2.2抑制劑、中和抗體使用資料 14 3.3 西方墨點法(western blot) 14 3.3.1 蛋白質萃取 14 3.3.2 配置膠體 14 3.3.3 電泳分析 15 3.3.4 蛋白質轉漬 15 3.3.5 抗體使用 15 3.3.6 顯影呈色 16 3.4 SAS細胞株MAT2A基因knockdown實驗 17 3.5 細胞增生速率測試 (Cell proliferation assay) 17 3.6 細胞存活率試驗 (MTT assay) 17 3.7 移動性試驗 (Migration assay) 18 3.8 侵襲性試驗 (Invasion assay) 18 3.9細胞聚球體形成試驗 (Sphere forming assay) 18 3.10 細胞聚球體MAT2A基因knockdown實驗 19 3.11 質體轉殖與建立過表現MAT2A的Ca922細胞株 19 第四章 結果 20 4.1 Arecoline 誘導SAS及Ca922細胞MAT2A蛋白質表現 20 4.2 Arecoline經由TGF-β路徑誘導SAS及Ca922細胞MAT2A蛋白質表現 20 4.3 TGF-β1誘導SAS及Ca922細胞MAT2A蛋白質表現 20 4.4 knockdown MAT2A可降低TGF-β1 induced的stemness markers表現 21 4.5 knockdown MAT2A蛋白可降低SAS細胞株移動與侵襲能力 21 4.6 MAT2A overexpression會增強Ca922細胞株的生長速度 21 4.7 SAS細胞聚球體(SAS spheres)中MAT2A蛋白表現量較高 22 4.8 knockdown MAT2A蛋白可降低SAS細胞形成聚球體的能力與幹細胞特性 22 4.9 MAT2A overexpression並不會增強stemness 及EMT markers的表現 23 4.10 使用MAT2A抑制劑 FIDAS-5可降低SAS細胞移動與侵襲能力 23 4.11 FIDAS-5可降低SAS細胞形成聚球體的能力與SAS sp細胞幹細胞特性 24 第五章、討論 25 第六章 圖與表 28 Reference 52 | |
| dc.language.iso | zh-TW | |
| dc.subject | 口腔癌 | zh_TW |
| dc.subject | 檳榔鹼 | zh_TW |
| dc.subject | 甲硫胺酸腺苷轉移酶2A | zh_TW |
| dc.subject | 轉化生長因子 | zh_TW |
| dc.subject | FIDAS-5 | zh_TW |
| dc.subject | 癌幹性 | zh_TW |
| dc.subject | FIDAS-5 | en |
| dc.subject | TGF-β1 | en |
| dc.subject | Arecoline | en |
| dc.subject | MAT2A | en |
| dc.subject | Oral cancer | en |
| dc.subject | Cancer stemness | en |
| dc.title | 口腔鱗狀上皮細胞癌幹細胞特性依賴MAT2A表現 | zh_TW |
| dc.title | MAT2A is required for stemness in oral squamous cell carcinoma | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 鄭世榮(Hsin-Tsai Liu),張瑞青(Chih-Yang Tseng) | |
| dc.subject.keyword | 口腔癌,甲硫胺酸腺苷轉移酶2A,檳榔鹼,轉化生長因子,FIDAS-5,癌幹性, | zh_TW |
| dc.subject.keyword | Oral cancer,MAT2A,Arecoline,TGF-β1,FIDAS-5,Cancer stemness, | en |
| dc.relation.page | 61 | |
| dc.identifier.doi | 10.6342/NTU202102421 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2021-08-18 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 口腔生物科學研究所 | zh_TW |
| dc.date.embargo-lift | 2026-08-16 | - |
| Appears in Collections: | 口腔生物科學研究所 | |
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| U0001-1708202110481100.pdf Restricted Access | 3.66 MB | Adobe PDF | View/Open |
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