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研究生:李易儒
研究生(外文):Yi-Ru Lee
論文名稱:長期酒精曝露模式探討肝癌細胞之生長週期與化療藥物之抗藥性研究
論文名稱(外文):Use of long term ethanol treatment to study the ethanol effect on cell cycle and chemosensitivity in hepatocellular carcinoma cell.
指導教授:何元順
指導教授(外文):Yuan-Soon Ho
學位類別:碩士
校院名稱:臺北醫學大學
系所名稱:醫學檢驗生物技術學研究所
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:70
中文關鍵詞:酒精肝癌細胞生長週期化療藥
外文關鍵詞:ethanolhepatocellular carcinoma cellcell cyclechemosensitivity
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Hepatitis B Virus (HBV)是亞洲常見的病毒性肝炎。長期酒精處理會導致肝細胞不正常增生,因此我們利用基因已被嵌入HBV genome,且持續表現HBsAg的肝癌細胞株Hep3B,在長期的酒精處理下,推測長期飲酒對肝癌病患及同時感染B肝病毒對細胞週期與抗藥性的影響。利用MTT技術與計數細胞的結果皆指出長期酒精培養會加速細胞生長。因此酒精可能改變及影響細胞的細胞週期與週期相關蛋白。結果顯示cyclin D1、cyclin D3是增加的。這與上述酒精增加細胞生長,有可能因為cyclin D1、D3蛋白增加,促進細胞往S期進行所產生的結果。進一步利用流式細胞儀分析酒精對細胞週期的影響,結果顯示酒精的作用明顯促進細胞週期的進行,且與G0/G1期的cyclin D1與cyclin D3蛋白變化有一致性。並進一步探討酒精是否增加或減少細胞對化療藥的敏感性。幾種臨床上常見的肝癌藥包含Cisplatin、Doxorubicin、Paclitaxel、Mitomycin C、5-Fluorouracil,觀察細胞在酒精處理下對各種化療藥的反應。結果顯示在這些化療藥中,酒精在48小時、2μg/ml的Cisplatin或10μM的Mitomycin C的處理下明顯增加細胞的耐受性。相反地,酒精增加細胞對Paclitaxel、Doxorubicin的敏感性。在合併Cisplatin與Mitomycin C,更增加酒精組細胞耐受性,但對細胞凋亡蛋白並未有顯著差異。此研究提供醫師在酗酒會影響治療肝癌同時感染B型肝炎病毒病人在化療治療效果的一些資訊。
Hepatitis B virus infection is common in south Asia and causes the hepatitis in human. Alcoholism causes the abnormal proliferation of hepatocytes, especially in chronic hepatitis patient or carrier. In order to investigate the effect of ethanol on the cell cycle and chemosensitivity of HBV-infected cells under the condition of the long-term ethanol treatment, the Hep3B cells were chosen as a study model, which are integrated with full length HBV genome and constitutively express HBsAg. By using the MTT technique and direct counting cell number, results appeared that long-term ethanol culture enhanced the cell growth. Therefore, ethanol might alter the cell cycle and cycle-related proteins. Under the treatment of ethanol, cyclin D1 and cyclin D3 were increased resulting in cells toward S phase. By using the flow cytometric technique, ethanol facilitated the progression of cell cycle, which is correlated to the alteration of cyclin D1 and cyclin D3. Because most chemodrugs were effective on the cell division, the sensitivity of chemodrugs of ethanol-treated Hep3B cells was also investigated. Clinically, cisplatin, doxorubicin, mitomycin C, paclitaxel and 5-fluorouracil were used for the treatment of liver cancer. Data appeared that ethanol increased the cells tolerance to cisplatin , mitomycin C ,or combination when cells were treated with 2 μg/ml cisplatin or 10μM Mitomycin C for 48 hours. But they had no differents on cell apoptosis protein. In constrast with paclitaxel or doxorubicin, ethanol could increase Hep3B cells the sensitivity to paclitaxel or doxorubicin. In conclusion, this study provided physicians the information that HBV-infected liver cancer patients could be influenced by alcoholism in chemotherapy.
中文摘要(Abstract in Chinese) I
英文摘要(Abstract in English) IV
目錄(Contents) VII
圖表目錄(Figures and Table list) X
縮寫表(Abbreviations) XII
第一章 前言 ( Introduction ) 1
(一)、肝與疾病 2
(二)、B 型病毒性肝炎 2
(三)、酒精性肝炎 3
(四)、酒精與肝細胞 5
(五)、酒精與 HBV病毒 5
(六)、細胞週期與細胞凋亡 6
(七)、常見臨床肝癌用藥與作用 9
(八)、實驗目的 10
第二章 材料與方法(Materials and Methods ) 11
藥品試劑 12
常用溶液 15
實驗方法 16
(一)、細胞株和細胞培養 16
(二)、MTT分析法 17
(三)、細胞週期分析 17
(四)、蛋白質萃取、分離與免疫墨點法 17
(五)、統計分析 20
第三章 結果(Results) 21
(一)、Hep3B 細胞株的特性與生長曲線 22
(二)、酒精對Hep3B細胞株的毒性 22
(三)、長期酒精曝露模式對Hep3B細胞株生長的影響 23
(四)、長期酒精曝露模式對細胞週期中G1、G1/S期蛋白的影響 24
(五)、長期酒精曝露模式對訊息傳導相關蛋白的影響 25
(六)、長期酒精曝露模式對細胞週期時間的影響 26
(七)、長期酒精曝露模式對化療藥的影響 27
(八)、長期酒精曝露模式對Cisplatin與Mitomycin C在細胞毒性與細胞凋亡蛋白的影響 28
第四章 討論(Discussion ) 29
第五章 圖與表(Figures and Tables ) 37
第六章 參考文獻(Reference) 52
附錄 59
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