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研究生: 余秀珊
Yu, Hsiu-Shan
論文名稱: 丁酸鈉(Sodium butyrate)抑制大腸癌細胞 Eps8的表現
Reduced Eps8 expression by sodium butyrate treatment in colorectal cancer cells
指導教授: 呂增宏
Leu, Tzeng-Horng
學位類別: 碩士
Master
系所名稱: 醫學院 - 藥理學研究所
Department of Pharmacology
論文出版年: 2002
畢業學年度: 90
語文別: 中文
論文頁數: 74
中文關鍵詞: 大腸癌細胞
外文關鍵詞: Eps8, sodium butyrate
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  • 中文摘要(Abstract in Chinese)
    食物纖維(dietary fiber)主要的成分之一的sodium butyrate(也是HDAC的抑制劑),具有抑制大腸癌細胞增生的能力。由於先前我們實驗室證實在v-Src癌化的細胞(IV5)內,Eps8兩個同原異質蛋白(p97kDa及p68kDa)表現量會增加,而且p97Eps8本身是一個致癌蛋白以及p97Eps8量的多寡會受到TSA(HDAC的抑制劑)的影響。因此我們想探討sodium butyrate抑制大腸癌細胞增生的機轉與p97EPS8之間是有何關係。由實驗結果我們發現sodium butyrate可以降低人類大腸癌細胞株(例如:Caco-2、SW480及SW620)的生長,而且其抑制細胞增生的作用呈現dose-dependent及time-dependent的現象。有趣地,我們也觀察到sodium butyrate可以降低p97Eps8的蛋白質及其mRNA表現量。在sodium butyrate抑制Eps8表現的同時,細胞內histone acetylation及p21 CIP1/WAF1的表達都有顯著增加。此外,sodium butyrate也會抑制細胞內FAK、Src, 以及b-catenin的表現。所以,我們認為sodium butyrate 之抑制大腸癌是因為除了增加p21 CIP1/WAF1的表達,同時也是由於許多與細胞生長相關的蛋白質受到抑制有關。

    英文摘要(Abstract in English)
    Sodium butyrate is a major component of dietary fiber as well as a HDAC inhibitor. Previous studies have indicated that it can inhibit cellular growth of the colon cancer cells. Since the expression of both p97Eps8 and p68Eps8 isoforms was elevated in v-Src transformed cells (IV5);p97Eps8 was an oncoprotein;and the expression of both p97Eps8 and p68Eps8 were inhibited by Tricostatin A(TSA, an inhibitor of histone deacetylase), we were interested in studying whether reduction of p97Eps8 expression is involved in sodium butyrate-mediated growth inhibition. In a series of studies, we observed that sodium butyrate could induce the expression of p21CIP1/WAF1 and result in the growth inhibition of the human colon cancer cell lines (i.e. Caco-2, SW480, SW620) in a dose- and time-dependent manner. And interestingly, both the protein and mRNA of eps8 gene were reduced in response to sodium butyrate. In addition to Eps8 protein, the expression of FAK, Src, and b-catenin were also reduced in these colon cancer cells. Therefore, in addition to the induction of p21CIP1/WAF1, reduction of several growth related proteins also contribute to the sodium butyrate-mediated growth inhibition in the human colon cancer cells.

    目錄 中文摘要 1 英文摘要 3 縮寫檢索表 5 第一章 緒 論 8 第二章 實驗材料及方法 第一節 實驗材料 19 第二節 實驗方法 23 第三章 實驗結果 35 第四章 討 論 43 圖 表 49 參考文獻 68

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