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研究生:黃郁文
研究生(外文):HUANG,YU-WEN
論文名稱:羥基芫花素之抗大腸癌功效及其機制探討
論文名稱(外文):Application of Hydroxygenkwanin for Colon Cancer Treatment and Investigation of Its Mechanisms
指導教授:王東弘陳琦媛陳琦媛引用關係
指導教授(外文):WANG,TONG-HONGCHEN,CHI-YUAN
口試委員:王東弘陳琦媛陳金銓呂彥禮
口試委員(外文):WANG,TONG-HONGCHEN,CHI-YUANCHEN,CHIN-CHUANLEU,YANN-LII
口試日期:2020-07-24
學位類別:碩士
校院名稱:長庚科技大學
系所名稱:健康產業科技研究所
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:2020
畢業學年度:108
語文別:中文
論文頁數:47
中文關鍵詞:大腸癌羥基芫花素細胞週期上皮-間質轉化組蛋白去乙醯酶
外文關鍵詞:Colorectal cancerHydroxygenkwaninCell cycleEpithelial mesenchymal transitionHistone deacetylase
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羥基芫花素(Hydroxygenkwanin, HGK)是由芫花花蕾萃取之類黃酮成分。目前對於羥基芫花素的生物活性所知仍非常有限,且並未有任何研究探討羥基芫花素在大腸癌之抗癌活性,在本研究中,我們運用不同濃度的羥基芫花素處理大腸癌細胞,發現細胞之增殖能力明顯受到抑制,並促使細胞週期停滯於G1 phase。我們進一步發現羥基芫花素可抑制CDK2及cyclin E等細胞週期調控蛋白之表達,因而導致細胞週期的停滯。此外,我們亦發現羥基芫花素可抑制上皮間質轉化蛋白Slug的表達而抑制細胞遷徙能力。在本研究中,我們除了初步證實羥基芫花素之抗大腸癌活性外,對其機制的探討亦有助於未來應用於臨床治療。

關鍵字:大腸癌、羥基芫花素、細胞週期、上皮-間質轉化、組蛋白去乙醯酶
Hydroxygenkwanin (HGK) is a flavonoid that is extracted from the buds of the deciduous shrub Daphne genkwa. Currently, there is limited knowledge on the biological activity of HGK. Additionally, there have not been any studies on the anticancer activity of HGK in colorectal cancer. In this study, we treated colorectal cancer cells with different concentrations of HGK and found that the proliferation ability of the cells was significantly inhibited and the cell cycle was arrested at G1 phase. We have further found that HGK can inhibit the expression of CDK2 and cyclin E, thus leading to cell cycle arrest. In addition, we also found that HGK can inhibit the expression of epithelial-mesenchymal transition protein slug and inhibit cell migration. In this study, we have preliminarily confirmed the anti-colorectal cancer activity of HGK and elucidated its mechanism of action. The findings of this study may be beneficial for future clinical treatment of colorectal cancer.

Keyword: Colorectal cancer, Hydroxygenkwanin, Cell cycle, Epithelial mesenchymal transition (EMT), Histone deacetylase(HDAC)
目錄
碩士學位論文指導教授推薦書
碩士學位論文口試審定書
中文摘要 i
英文摘要 ii
目錄 iii
第一章 緒論 1
第一節 大腸癌簡介 1
第二節 癌症與上皮-間質轉化(Epithelial-Mesenchymal Transition,EMT) 3
第三節 癌症與組蛋白去乙醯酶 (Histone deacetylase,HDAC) 5
第四節 組蛋白去乙醯酶(HDAC)與細胞週期調控 7
第五節 芫花與癌症 8
第二章 研究動機、目的及實驗設計 11
第一節 研究動機 11
第二節 實驗設計 11
第三章 材料與方法 13
第一節 細胞株及培養 (Cell lines and cell culture) 13
第二節 藥物及抗體 (Drug and Antibodies) 14
第三節 細胞增殖試驗 (Cell proliferation assay ) 14
第四節 細胞計數 (Cell counting) 15
第五節 流式細胞儀分析 (Flow cytometric analysis) 15
第六節 傷口癒合試驗 (Wound healing assay) 16
第七節 TUNEL細胞凋亡檢測試驗(Terminal deoxynucleotidyl transferase dUTP nick end labeling assay) 17
第八節 蛋白質萃取及定量 (Protein extraction and quantification) 17
第九節 西方墨點法 (Western blot) 18
第十節 動物實驗 (Xenograft model) 20
第十一節 統計分析 (Statistical analysis) 20
第四章 結果 21
第一節 探討羥基芫花素對於大腸癌細胞株之抑制效果 21
第二節 羥基芫花素對於大腸癌細胞株細胞週期之影響 21
第三節 羥基芫花素對於大腸癌細胞株細胞週期相關蛋白表現之影響 22
第四節 羥基芫花素對於大腸癌細胞株凋亡之影響 23
第五節 羥基芫花素對於大腸癌細胞株爬行能力之影響 23
第六節 羥基芫花素對於上皮-間質轉化相關蛋白表現之影響 24
第七節 羥基芫花素對於大腸癌細胞株與組蛋白去乙醯酶的影響 24
第八節 動物模型驗證羥基芫花素對於腫瘤生長之影響 25
第五章 討論 26
第六章 圖表 29
第七章 參考文獻 43


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