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研究生:詹雅玲
研究生(外文):Ya-Ling Chan
論文名稱:探討四物湯萃取物對卵巢癌與前列腺癌之作用
論文名稱(外文):Studying the effects of the traditional Chinese medicineFour-Agents-Decoction on ovarian and prostate cancers
指導教授:高銘欽高銘欽引用關係
指導教授(外文):Ming-Ching Kao
學位類別:碩士
校院名稱:中國醫藥大學
系所名稱:生物科技學系碩士班
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:中文
論文頁數:91
中文關鍵詞:四物湯當歸川芎白芍熟地黃卵巢癌前列腺癌醛酮還原酶1C類固醇5α還原酶
外文關鍵詞:Four-Agents-DecoctionOvarian CancerProstate CancerAKR1CSRD5A
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四物湯為傳統中藥複方,由當歸、川芎、白芍、熟地黃組成。此方源遠流長,在亞洲地區廣泛應用於補血和治療婦科疾病。最近研究指出,四物湯能夠有效的緩解經痛且無任何副作用產生。在社會大眾普遍認知下,四物湯是婦女的健康享用權。然而,這種情況可能要改觀,並延伸擴展到男性的健康層面上。我們初步研究結果顯示,四物湯水萃物對人類卵巢癌細胞株的生長具有抑制效果,並經過裸鼠動物實驗結果證實。本論文也證實四物湯水萃物具有抑制人類前列腺癌細胞株的生長作用。此外,我們利用基因體生物反應指紋分析技術,結果顯示四物湯水萃物處理前列腺癌細胞株後的基因圖譜具有高植物相似度指數,確定四物湯水萃物品質的一致性。進一步以生物資訊分析四物湯水萃物作用的細胞路徑並加以驗證,結果發現AKR1C和SRD5A基因都與代謝相關,並可能在四物湯水萃物對前列腺癌細胞中具有調控的功能。AKR1C和SRD5A在雄性激素代謝的訊息傳遞路徑中是很重要的基質。研究的最終目標是要解開四物湯影響卵巢癌和前列腺癌之抑制細胞增生的可能機制,並提供一個治療卵巢癌和前列腺癌的替代方法。
The traditional Chinese medicine Four-Agents-Decoction (FAD; also known as Si-Wu-Tang, SWT) is composed of Angelicae Sinensis Radix, Chuanxiong Rhizoma, Paeoniae Albae Radix, and Rehmanniae Radix. This formula has been used for centuries as a remedy for nourishing the blood and treating women’s diseases in Asian countries. Recent reports indicate that FAD is capable of reducing menorrhalgia efficiently without any side effects. In general, FAD is known to be a privilege for woman’s health. However, this situation may have to be reconsidered and extended to man’s health. We have discovered that FAD extract (FADE) has growth inhibition effect on human ovarian cancer cells. The growth inhibition effect on human ovarian cancer cells has also been confirmed via a nude mouse model. In this thesis, we also demonstrate the growth suppression effect of FADE on human prostate cancer cells. Furthermore, the Genomic Bioresponse Fingerprint profiling followed by evaluating the Phytomics Similarity Index was used to control the quality of FADE. In addition, possible FADE-mediated cellular networks were obtained through bioinformatics analysis. These results reveal that AKR1C and SRD5A may be modulated in the presence of FADE in prostate cancer cells. AKR1C and SRD5A are known to be the important substrates of the androgen metabolic pathway. The final goal of this study is to unravel possible mechanisms of anti-proliferation effects FADE on ovarian and prostate cancer cells, and provide an alternative method against ovarian and prostate cancers.
中文摘要.............................................. I
Abstract...............................................II
誌謝..................................................III
目錄....................................................V
表目錄...............................................VIII
圖目錄.................................................IX
附錄目錄...............................................XI
縮寫表................................................XII
第一章 前言...........................................1
第一節、 研究背景與目的.................................1
第二節、 四物湯.........................................2
壹、 四物湯的起源...................................2
貳、 四物湯的組成與功用 .............................3
參、 四物湯的藥理功效與近代研究.....................3
第三節、 卵巢癌.........................................4
第四節、 前列腺癌.......................................5
第五節、 基因體生物反應指紋圖譜(Genomic Bioresponse Fingerprinting)..........................................8
第二章 研究材料與方法.................................11
第一節、 實驗材料及操作儀器.............................11
壹、 細胞株.........................................11
貳、 中藥複方劑—四物湯 .............................12
參、 抗體...........................................13
肆、 藥品與試劑.....................................14
伍、 主要儀器.......................................17
第二節、 實驗方法.......................................18
壹、 細胞株培養(Cell Culture).......................18
一、 解凍細胞.......................................18
二、 繼代培養細胞...................................18
三、 冷凍細胞.......................................18
貳、 四物湯萃取(Extraction of Four-Agents-Decoction) ...............................................19
參、 細胞毒性測試(Trypan Blue Assay)................19
肆、 細胞密度分析(Cell Density Assay)...............20
伍、 細胞存活率分析(MTT Assay)......................20
陸、 動物實驗(Animal test)..........................21
一、 動物來源.......................................21
二、 動物飼養.......................................21
三、 皮下腫瘤誘發...................................21
四、 給藥劑量.......................................22
五、 給藥途徑.......................................23
六、 動物犧牲與檢體之收集與分析.....................23
柒、 核糖核酸的萃取(Isolation of total RNA).........23
捌、 基因微陣列與生物反應指紋圖譜分析(Affymetrix GeneChip and Genomic Bioresponse Fingerprinting analysis) ...............................................24
玖、 生物資訊分析細胞路徑(GeneGo MetaCoreTM)........24
壹拾、 西方墨點法(Western Blotting)...................25
壹拾壹、 反轉錄酶聚合酶連鎖反應(RT-PCR).................25
壹拾貳、 即時反轉錄酶聚合酶連鎖反應(Real-Time PCR)......26
壹拾參、 酵素連結免疫吸附法(ELISA assay)................27
壹拾肆、 統計分析 (Statistical Analysis)................27
第三章 結果...........................................28
第一節、 四物湯萃取物對於卵巢癌細胞株的影響.............28
壹、 四物湯水萃物抑制SKOV-3卵巢癌細胞株之生長.......28
貳、 四物湯乙酸乙酯層萃物抑制SKOV-3卵巢癌細胞株之生長 ...............................................28
參、 在裸鼠實驗觀察到四物湯水萃物可抑制SKOV-3卵巢癌細胞株誘導之異種移植腫瘤生長................................28
肆、 在裸鼠實驗觀察到四物湯乙酸乙酯層萃物可抑制SKOV-3卵巢癌細胞株誘導之異種移植腫瘤生長........................29
伍、 四物湯水萃物及四物湯乙酸乙酯層萃物之安全性測試 ...............................................30
第二節、 四物湯水萃物對前列腺癌細胞株的影響.............30
壹、 四物湯水萃物抑制LNCaP前列腺癌細胞株之生長......30
貳、 四物湯水萃物抑制DU-145前列腺癌細胞株之生長.....31
參、四物湯水萃物抑制PC-3前列腺癌細胞株生長..............31
第三節、 四物湯水萃物對LNCaP前列腺癌細胞株的基因體生物反應指紋圖譜分析............................................32
壹、 四物湯水萃物品質控管...........................32
貳、 四物湯水萃物影響細胞內生物反應之基因變化.......33
第四節、 生物資訊學推測四物湯水萃物影響LNCaP前列腺癌細胞株可能的細胞路徑..........................................33
第五節、 四物湯水萃物可能藉由調節AKR1Cs蛋白表現進而抑制LNCaP前列腺癌細胞株之生長...............................35
第六節、 四物湯水萃物影響DHT相關合成代謝基因之mRNAs表現量 ........................... ....................35
第七節、 四物湯水萃物影響DHT的表現量 ....................36
第四章 討論............................................38
第一節、 四物湯水萃物及四物湯乙酸乙酯層萃物對人類卵巢癌細胞之體內及體外抑制生長.....................................38
第二節、 PhytomicsQC指紋分析平台在中草藥研究的應用與意義 ...............................................39
第三節、 四物湯水萃物影響前列腺癌細胞的細胞路徑.........40
第四節、 四物湯水萃物影響DHT相關合成代謝基因............40
第五節、 四物湯水萃物可做為未來卵巢癌與前列腺癌之前瞻性藥
物參考..........................................42
第五章 結論............................................43
第六章 參考文獻........................................44
第七章 圖表............................................50
第一節、 表..............................................50
第二節、 圖..............................................56
附錄.....................................................84
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