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研究生:宋景陽
研究生(外文):sung jing yung
論文名稱:蛋白質體分析紅麴菌monacolinK和butyrate協同誘導Caco-2腫瘤細胞株凋亡
論文名稱(外文):Proteomic analysis of drug-induced apoptosis in Caco-2 cancer cell line by Monascus-productive monacolin K with butyrate
指導教授:林文源林文源引用關係
學位類別:碩士
校院名稱:實踐大學
系所名稱:食品營養研究所
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:中文
論文頁數:74
中文關鍵詞:monacolin Kbutyrate二維電泳
外文關鍵詞:monacolin KbutyrateTwo-dimentional electrophoresis
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Monacolin K屬於statin類藥物為HMG-CoA 還原酶抑制子,藉由抑制HMG-CoA 還原酶活性進而抑制HMG-CoA合成膽固醇,普遍作為膽固醇的調控藥物。相關研究指出statin 有抑制腫瘤細胞活性的作用,推論statin會抑制腫瘤細胞進入增生週期,活化腫瘤抑制蛋白的活性。butyrate為腸道微生物的發酵產物,和statin有協同抑制腫瘤細胞活性誘導細胞凋亡。在本研究中利用蛋白質體分析系統分析monacolin K和butyrate處理Caco-2腫瘤細胞誘導腫瘤細胞活性和誘導細胞凋亡的趨勢,顯微鏡觀察分析monacolin K和butyrate處理腫瘤細胞對腫瘤細胞的形態變化,二維蛋白質膠體電泳分析藥物處理對腫瘤細胞的蛋白質表現的變化。研究中獲得20個可能和monacolin K誘導細胞凋亡的相關蛋白質,為cytokeratin家族、Peroxiredoxin家族、GSTP1-1等。cytokeratin家族和GSTP1-1在相關研究已證實和腫瘤活性的表現有關,以西方墨點法分析,cytokeratin 家族和GSTP1-1確實受monacolin K和butyrate的調控,monacolin K和butyrate對腫瘤細胞蛋白質表現具有偕同抑制。
Monacolin K for statin family of medicine is inhibitor for HMG-CoA reductase. Monacolin K limit cholesterol synthesis by suppressing HMG-CoA reductase Activation, is generally regard as the regulation and control medicine of the cholesterol. There is function which suppress tumour cell's activation on relevant research point out statin, inference statin will suppress the tumour cell to start cell hyperplasia cycle, and activates the activation that the tumour suppresses the albumen. Butyrate is a fermented product of the intestinal microorganism, and statin suppresses tumour cell's activation to lead cells to wither to die in coordination. Utilize proteomic analysis monacolin K and butyrate induce Caco-2 tumour cell death and apoptotic. The microscope observes analyses monacolin K and butyrate deal induce tumour cell's shape change. Two-dimentional protein colloid electrophoresis analyse medicine deal induce protein expression change in tumour cell. We get 20 relevant proteins that may lead cells to wither and die with monacolin K while studying, it is cytokeratin family, Peroxiredoxin family, and GSTP1-1. Cytokeratin family and GSTP1-1 have already in relevant research verified that has been involved in behavior of the tumour activation, west blot analysis expression, cytokeratin family and GSTP1-1 really receive the regulation and control of monacolin K and butyrate, there are monacolin K and butyrate together with suppressing to that the tumour cell protein behave.
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目 錄
中文摘要.........................I
英文摘要.........................II
前 言...........................1
文獻回顧.........................2
一、statin類藥物和膽固醇類生合成的相關研究........2
二、腫瘤發生誘導機制..................2
三、P21、P27蛋白質...................4
四、c-Myc蛋白質....................5
五、細胞凋亡誘導....................5
六、 Statin和腫瘤細胞活性抑制和雕亡誘導的相關研究....6
七、 monacolin K的相關研究...............7
八、butyrae 和腫瘤相關性研究...............8
九、Caco-2細胞株在相關研究的運用............8
十、二維蛋白質膠體膠體電泳的運用與目的.........9
研究目的.........................11
研究目標.........................11
材料與方法........................12
細胞模式........................12
一、Caco-2腫瘤細胞株培養................12
二、細胞繼代培養....................12
三、細胞保存與活化...................13
四、藥物處理模式....................13
五、細胞內毒性試驗...................14
六、二維蛋白質膠體電泳細胞蛋白質樣品製備........14
七、二維蛋白質膠體電泳蛋白質定量............14
二維電泳分析實驗....................15
一、一維蛋白質膠體電泳樣品前處理............ 15
二,一維蛋白質膠體電泳.................15
三、梯度SDS電泳膠片的製作..............16
四、二維蛋白質膠體電泳(SDS-PAGE)..........16
五、二維白質膠體電泳膠片染色..............17
六、二維白質膠體電泳膠片影像分析............18
七、膠體內蛋白質分解(In-gel digestion for SYPRO ruby stain).19
八、蛋白質身分鑑定(MALDI-TOF/TOF)..........19
九、SDS PAGE細胞蛋白質樣品製備............20
SDS PAGE 蛋白質膠體電泳................20
一、SDS PAGE細胞蛋白質樣品製備............20
二、SDS PAGE 蛋白質濃度定量..............20
三、SDS PAGE蛋白質膠體電泳..............21
西方墨點法........................22
結果...........................23
一、顯微觀察藥物影響Caco-2腫瘤細胞型態變化......23
二、MTT試驗分析...................24
三、二維蛋白質膠體電泳膠片分析.............26
四、蛋白質表現與身分鑑定................26
五、西方墨點法分析...................28
1. Monacolin K單一處理................28
2.Monacolin K 和butyrate 共同處理...........29討論...........................31
結論...........................36
參考文獻.........................61
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