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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 郭彥彬(Yen-Ping Kuo) | |
dc.contributor.author | Yi-Xuan Pan | en |
dc.contributor.author | 潘奕璇 | zh_TW |
dc.date.accessioned | 2021-06-08T01:56:39Z | - |
dc.date.copyright | 2020-08-27 | |
dc.date.issued | 2020 | |
dc.date.submitted | 2020-08-18 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19387 | - |
dc.description.abstract | 根據國民健康署108年的統計,口腔癌居台灣男性十大癌症中死亡率第四位,平均發生年齡為發生率前五名癌症中最年輕的,是癌症死亡年增率最高的癌症。嚼食檳榔已經被證實為導致台灣口腔癌發生最主要的危險因子。檳榔鹼arecoline是檳榔中最主要的興奮成分,在唾液中的濃度可達0.9mM。NPM1 (Nucleophosmin 1)參與DNA之複製、轉錄與修復、細胞週期、蛋白修飾、細胞凋亡等。我們實驗室先前發現NPM1在口腔癌組織表現較高。NPM1的表現量和患者的腫瘤大小(T status)、淋巴結轉移 (N status)有統計上的正相關。且NPM1的表現量較高者其存活時間較短。本研究發現以0.4mM arecoline處理人類牙齦上皮SG細胞株,口腔癌SAS細胞株與FaDu細胞株都會誘導NPM1蛋白的表現。加入TGF-β中和抗體可抑制由arecoline所誘導的NPM1蛋白的表現量,表示arecoline是經由TGF-β來誘導NPM1蛋白的表現。癌症幹細胞是造成癌症轉移、復發,或是腫瘤對於化療、放射性療法產生抗性的原因之一。近年發現上皮-間質轉換(EMT)可以誘發癌細胞產生幹細胞特性。是腫瘤晚期惡化與轉移的原因之一。本研究以FaDu細胞株轉殖NPM1質體,cell migration assay分析發現可增加FaDu細胞株的移動。大量表現NPM1會增加上皮-間質轉換標記蛋白E-cadherin表現量下降、N-cadherin、ZEB1、Vimentin、Slug、Snail、Twist表現量上升;幹細胞標記蛋白(stemness marker) CD133、CD44、KLF4、Oct4A、Nanog表現量上升及增加形成球體(sphere)的能力。NPM1抑制劑例如: NSC348884 具有治療口腔癌及改善臨床不良預後的潛力。 | zh_TW |
dc.description.abstract | According to the 2017 statistics of Health Promotion Administration, oral cancer ranks fourth in the fatality rate of male sufferer in Taiwan, and the cancer with the highest annual growth rate of mortality. The frequent use of areca nut preparations is a significant risk factor for the development of oral cancer. We recently showed higher NPM1 (Nucleophosmin 1) expression was significantly correlated with larger tumor size, nodal metastasis. Multivariate analysis revealed that higher NPM1 expression were an unfavorable independent factor for survival. Arecoline, the major areca nut alkaloid, induced the expression of NPM1 in oral epithelial cell SG, SAS and FaDu cell line at concentration of 0.4 mM . TGFβ-neutralizing antibody completely inhibited the arecoline-induced NPM1 expression. Overexpression of NPM1 stimulated the migration and sphere formation of Fadu cells in vitro. Overexpression of NPM1 increased stemness marker such as CD133、CD44、KLF4、Oct4A、Nanog and epithelial-mesenchymal transition (EMT)-related protein N-cadherin、ZEB1、Vimentin、Slug、Snail、Twist expression. lnhibiting the arecoline-induced NPM1signaling could provide an alternative therapeutic apporach for the treatment of oral cancer. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T01:56:39Z (GMT). No. of bitstreams: 1 U0001-1708202011144800.pdf: 3020915 bytes, checksum: 1cf4b6ae010c5d423792ed2eda49103d (MD5) Previous issue date: 2020 | en |
dc.description.tableofcontents | 致謝 iii 目錄 iv 中文摘要 vii Abstract viii 導論 1 1.1口腔癌 1 1.1.1口腔癌之流行病學 1 1.1.2口腔癌之病理學 1 1.1.3口腔癌治療 1 1.1.4口腔癌之危險因子 2 1.2NPM1(Nucleoplasmin1)蛋白概論 3 1.2.1NPM1的簡介 4 1.2.2NPM1的癌症中扮演的角色 4 1.2.3NPM1訊息傳導及基因調控 5 1.3轉型生長因子β(Transforming growth factor β) 6 1.3.1TGF-β的簡介 6 1.3.2TGF-β的訊息傳遞路徑 6 材料與方法 8 2.1細胞株與細胞培養 8 2.2藥物處理 8 2.2.1 Arecoline的處理 8 2.2.2 TGF-β的處理 8 2.2.3 Inhibitor使用資料 9 2.3西方墨點法 9 2.3.1蛋白質萃取 9 2.3.2蛋白質濃度測定 9 2.3.3膠體配置與電泳分析 10 2.3.4蛋白轉漬 10 2.3.5抗體的使用與顯影呈色 11 2.4細胞轉染 12 2.4.1FaDu細胞snail knockdown 12 2.5球形成試驗(sphere-forming assay) 12 2.6細胞聚球體形成試驗(colony formation assay) 12 2.7細胞移動分析(Cell migration assay) 12 2.8細胞侵襲分析(Cell invasion assay) 13 2.9成長曲線分析(Growth Curve Analysis) 13 結果 14 3.1 Arecoline誘導口腔上皮細胞中NPM1蛋白的表現 14 3.2口腔癌細胞株中Arecoline經由TGF-β誘導NPM1蛋白的表現 14 3.3 TGF-β可誘導口腔細胞株中NPM1蛋白的表現 14 3.4 NPM1蛋白的過表現會增加FaDu細胞株細胞移動的能力 15 3.5 FaDu細胞聚球體增加NPM1蛋白的表現 15 3.6 NPM1蛋白過表現增加FaDu細胞株幹細胞特性 16 3.7 NPM1蛋白過表現增加FaDu細胞株上皮間質轉換標誌蛋白的表現量 16 3.8 Snail在NPM1 誘導的 stemness 及 EMT扮演重要的角色 16 3.9 過度表現NPM1的FaDu細胞株會增加pSmad3的表現量 17 討論 18 圖與表 20 Reference 37 | |
dc.language.iso | zh-TW | |
dc.title | 檳榔鹼arecoline經TGF-β訊息傳遞路徑誘導口腔上皮細胞中NPM1表現之研究 | zh_TW |
dc.title | Arecoline induces NPM1 expression through TGF-β signaling in oral epithelial cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 108-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 鄭世榮(Shih-Jung Cheng),張瑞青(Rui-Qing Zhang) | |
dc.subject.keyword | 口腔癌,檳榔鹼,TGF-β,NPM1, | zh_TW |
dc.subject.keyword | Oral cancer,Arecoline,TGF-β,NPM1, | en |
dc.relation.page | 41 | |
dc.identifier.doi | 10.6342/NTU202003697 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2020-08-18 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 口腔生物科學研究所 | zh_TW |
顯示於系所單位: | 口腔生物科學研究所 |
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