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系統識別號 U0007-1108201515254000
論文名稱(中文) 異甘草素對人類子宮內膜癌及卵巢癌細胞生長及移行能力之抑制效果
論文名稱(英文) Inhibitory Effects of Isoliquiritigenin on the Proliferation and Migration of Human Endometrial Cancer and Ovarian Cancer Cells
校院名稱 臺北醫學大學
系所名稱(中) 保健營養學研究所
系所名稱(英) Graduate Institute of Nutrition and Health
學年度 103
學期 2
出版年 104
研究生(中文) 陳欣媛
研究生(英文) Hsin-Yuan Chen
學號 M507102021
學位類別 碩士
語文別 中文
口試日期 2015-07-09
論文頁數 102頁
口試委員 委員-江文章
委員-謝榮鴻
委員-謝宗明
共同指導教授-黃翠琴
指導教授-夏詩閔
中文關鍵字 子宮內膜癌  卵巢癌  異甘草素  細胞凋亡  細胞自噬 
英文關鍵字 Endometrial cacer  Ovarian cancer  Isoliquiritigenin  Apoptosis  Autophagy 
學科別分類
中文摘要 子宮內膜癌 (endometrial cancer)及卵巢癌 (ovarian cancer)好發於停經後的婦女,在歐美國家是常見的癌症,在台灣因女性普遍使用賀爾蒙補充治療,其發生率也攀升至婦科癌症的第一名。近幾年西方國家開始普遍使用中草藥療法,異甘草素 (isoliquiritigenin, ISL)為從甘草植物中萃取出之黃酮類 (flavonoid)活性化合物,先前的研究結果發現,異甘草素具有抗氧化、抗發炎以及抑制腫瘤的效果,而本研究想要探討異甘草素對人類子宮內膜癌及卵巢癌細胞的抗腫瘤效果。分別利用子宮內膜癌細胞株HEC-1A、RL95-2及卵巢癌細胞株OVCAR5和ES-2進行研究,分別介入異甘草素後,觀察其細胞增生、細胞週期、細胞凋亡 (apoptosis)和細胞自噬 (autophagy)相關蛋白之表現量,最後以傷口癒合試驗來觀察異甘草素對癌細胞的抑制效果。實驗結果發現:1. 異甘草素不管在劑量效應還是時間效應上,都能夠顯著抑制癌細胞的生長;2. 異甘草素能夠造成細胞週期停滯於G2/M期;3. 異甘草素會促進細胞凋亡及細胞自噬作用相關蛋白LC3BⅡ的表現量增加;4. 異甘草素會抑制子宮內膜癌細胞的移行能力 (migration)。從本研究結果可以得知,異甘草素對於抑制子宮內膜癌及卵巢癌細胞生長具有多重效果,在治療子宮內膜癌及卵巢癌方面非常具有潛力。
英文摘要 Endometrial cancer and ovarian cancer occurs in women after menopause, is the most common cancer in women in the United States. In Taiwan, due to the widespread use of hormone replacement therapy, the incidence of gynecologic cancer climbed to first name. In recent years, Western countries began the widespread use of herbal therapies, Isoliquiritigenin (ISL), one of the active components in licorice plant flavonoids, in past study, ISL have antioxidantion, anti-inflammatory and tumor suppression effect. In this study, we investigated the antitumor effect of ISL on human endometrial cancer and ovarian cancer cell in vitro. HEC-1A and RL95-2 endometrial cancer cell lines and OVCAR5 and ES-2 ovarian cancer cell lines were used as targets. We examined the effects of ISL on cell proliferation, cell cycle regulation and apoptosis or autophagy related protein expression. Further, we investigated the effects of ISL on migration of cancer cells. ISL significantly inhibited the proliferation of cancer cell lines in a dose-dependent and time-dependent manner. Flow cytometry analysis indicated that ISL induced G2/M phase arrest. ISL enhanced the expression of LC3BⅡ protein associated with autophagy. Further, ISL inhibited migration of cancer cells. These findings suggest that ISL is a candidate agent for the treatment of endometrial cancer and ovarian cancer.
論文目次 中文摘要 .................................................I
Abstract ................................................II
謝誌.....................................................III
目錄......................................................IV
圖目次....................................................VI
表目次..................................................VIII
第一章、 緒論.............................................1
第一節、 研究動機與目的...................................1
第二節、 研究架構.........................................2
第二章、 文獻回顧.........................................3
第三節、 子宮內膜癌.......................................3
1. 導論.............................................3
2. 子宮生理構造.....................................6
3. 危險因子.........................................7
4. 症狀與診斷......................................11
5. 分期與組織學分類................................12
6. 預後............................................16
7. 治療............................................16
8. 復發............................................16
第四節、 卵巢癌..........................................17
1. 導論............................................17
2. 危險因子........................................19
3. 症狀與診斷......................................19
4. 分期與組織學分類................................19
第五節、 異甘草素 (Isoliquiritigenin, ISL)...............22
第六節、 細胞死亡途徑....................................26
第七節、 可能參與的機制..................................30
第三章、 實驗設計與材料方法..............................36
第一節、 試劑與材料 (reagent and material)...............36
第二節、 異甘草素 (isoliquiritigenin)的製備..............37
第三節、 人類子宮內膜癌及卵巢癌細胞之培養 (cell culture) ................................................37
第四節、 細胞存活率分析 (cell viability analysis)........38
第五節、 細胞計數 (cell counting).......................39
第六節、 細胞週期分析 (cell cycle analysis)..............39
第七節、 細胞凋亡分析 (apoptosis analysis)...............40
第八節、 西方轉漬法 (western blot).......................40
第九節、 傷口癒合試驗 (wound healing assay).............43
第十節、 統計分析........................................43
第四章、 結果............................................44
第一節、 異甘草素對子宮內膜癌及卵巢癌細胞的細胞毒性試驗 ................................................44
第二節、 異甘草素對子宮內膜癌及卵巢癌細胞株的抗增生之效果 ................................................45
第三節、 異甘草素誘發子宮內膜癌及卵巢癌細胞的細胞週期停滯於G2/M期 ...................................................46
第四節、 異甘草素誘發子宮內膜癌和卵巢癌細胞的凋亡........47
第五節、 異甘草素對子宮內膜癌及卵巢癌細胞的細胞凋亡相關蛋白表現量之影響..............................................48
第六節、 不同的異甘草素劑量對子宮內膜癌及卵巢癌細胞的細胞自噬相關蛋白表現量之影響....................................50
第七節、 合併給予細胞自噬抑制劑及異甘草素,對子宮內膜癌及卵巢癌細胞的細胞凋亡及細胞自噬相關蛋白表現量之影響..........53
第八節、 異甘草素降低子宮內膜癌細胞的移行能力............54
第五章、 討論............................................55
第一節、 異甘草素對於子宮內膜癌和卵巢癌細胞的抑制效果....55
第二節、 異甘草素誘發的細胞凋亡..........................57
第三節、 異甘草素誘發的細胞自噬..........................58
第四節、 異甘草素與細胞自噬抑制劑........................60
第六章、 結論............................................62
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