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研究生: 蔡孟珊
Tsai, Meng-Shan
論文名稱: 研究Eps8參與在COX-2所媒介的大腸直腸癌 的癌症生成
Participation of Eps8 in COX-2-mediated colorectal cancer formation
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: 2006
畢業學年度: 94
語文別: 中文
論文頁數: 81
中文關鍵詞: 大腸癌
外文關鍵詞: PGE2, Eps8, COX-2, colorectal cancer
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  • 在我們實驗室先前的研究中發現,在人類的大腸直腸癌細胞株中,Eps8有大量表達的情形;而我們也知道COX-2在大腸癌化過程中扮演了一個重要的角色。因此為了進一步了解Eps8和COX-2在人類大腸直腸癌中的相互關係,首先我們觀察Eps8是否會影響COX-2的表現。結果我們發現無論是Eps8 overexpression或是Eps8 knockdown的人類大腸直腸癌細胞,COX-2的mRNA和蛋白質表現皆不會受到影響。相反的,我們發現利用NS398 (COX-2專一性抑制劑)而非SC560 (COX-1專一性抑制劑),會明顯的降低SW620的Eps8之蛋白質及mRNA的表現。我們進一步利用不同的人類大腸直腸癌的細胞株,包含了SW480、SW620、HCT116、HT29、LS174T及WiDr,發現大多的細胞株皆會受NS398的作用而抑制Eps8的表現。而在細胞生長的實驗中,我們也觀察到在NS398的藥物作用之下,SW620的細胞生長也會隨著藥物濃度及時間的增加而被抑制。我們進一步用不同的prostaglandins來處理SW480後,發現Eps8的蛋白質表現會被誘導上升。經由以上的實驗結果,我們認為COX-2可能會透過Eps8而參與在人類大腸癌的癌症生成之中。

    Our previous studies indicate that the expression of Eps8 is elevated in human colorectal cancer cell. To further understand the relationship between Eps8 and COX-2 in colorectal Eps8 and COX-2. We observed no effects on COX-2 mRNA and protein level by Eps8 overexpression or Eps8 attenuation in human colorectal cancer cell. In contrary, when COX-2 activity was reduced by NS398 (a COX-2 specific inhibitor), but not by SC560 (a COX-1 specific inhibitor), we observed significant decrease of Eps8 expression and mRNA level in SW620 cells. Furthermore, we used different human colorectal cancer cell lines, included SW480, SW620, HCT116, HT29, LS184T and WiDr, and found that NS398 can reduce Eps8 expression in almost all colorectal cancer cell lines. We also found that NS398 can inhibit SW620 cellular growth in time-dependent and dose-dependent manners. Moreover, we treated SW480 cells with several prostaglandins and found that Eps8 was induced. Therefore, COX-2 may involve in human colorectal cancer formation through Eps8.

    頁數 中文摘要 3 英文摘要 5 縮寫檢索表 7 第一章 緒論 9 第二章 實驗材料及方法 22 第一節 實驗材料 23 第二節 實驗方法 27 第三章 實驗結果 40 第四章 討論 47 第五章 圖表 53 參考文獻 63 附錄 74 自述 81

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