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研究生:江伊琁
研究生(外文):Yi-Hsuan Chiang
論文名稱:探討 dihydrosinularin 對非小細胞肺癌之作用及其機轉探討
論文名稱(外文):To explore the effects of dihydrosinularin in non-small cell lung cancer and its underlying mechanism
指導教授:林季千
口試委員:陳與國羅至佑
口試日期:2017-06-27
學位類別:碩士
校院名稱:國立中興大學
系所名稱:生命科學院碩士在職專班
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:中文
論文頁數:49
中文關鍵詞:dihydrosinularin非小細胞肺癌細胞凋亡細胞週期細胞自噬
外文關鍵詞:dihydrosinularinnon-small cell lung cancer(NSCLC)apoptosiscell cycleautophagy
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此次的研究,我們利用養殖型軟珊瑚Sinularia flexiblis分離出的二萜類,dihydrosinularin探討對於人類非小細胞肺癌細胞株CL1-5及H226之毒性功效及其可能之作用機轉,而實驗結果顯示,dihydrosinularin會隨著劑量提升抑制細胞增殖。此外,我們的結果也顯示dihydrosinularin可能會經由造成DNA損傷進而引發G2/M細胞週期停滯。西方點墨法結果指出dihydrosinularin經由調控p-H2A.X、p-ATM、p-Chk2途徑,引發DNA損傷,並且下調細胞週期蛋白p-cdc25c (Ser216) 及cyclin B1的表現,進一步我們也發現,使用較高濃度的dihydrosinularin處理細胞,有明顯細胞凋亡的現象,在48小時後PARP剪切片段表現有增加趨勢。總結來說,此次研究證明dihydrosinularin具有對抗人類非小細胞肺癌的活性,且可能可作為新的治療非小細胞肺癌的候選藥物。
In this study, we evaluated the cytotoxic effect of dihydrosinularin, an active compound isolated from the cultured soft coral Sinularia flexibilis, on the human non-small cell lung cancer cells (NSCLC), CL1-5 and H226, and to subsequently explore the underlying molecular mechanisms. From the results of our study, cell viability was obviously inhibited by dihy-drosinularin in a dose-dependent manner. In addition, our results suggested that dihydrosinularin triggered DNA damage and subsequently induced cell cycle G2/M arrest. Western results further showed that dihydrosinularin can up-regulated p-H2A.X, p-ATM, p-Chk2, and p-cdc25c (Ser216) expression coupled with down-regulated cyclin B1 expression. Moreover, we also ob-served that cell apoptosis induced by a high dose of the dihydrosinularin. After 48 hr treatment, increased expression of cleaved PARP was observed. Taken together, our findings demonstrated that dihydrosinularin possesseed anti-NSCLC activity, and therefore is a potential candidate for NSCLC treatment.
目錄
摘要 i
Abstract ii
目錄 iii
圖表目錄 v
緒論 1
一、 肺癌 1
二、 海洋提取物之應用 3
三、 研究目的 6
材料及方法 7
一、 天然物化學製品 7
二、 細胞株及培養條件 7
三、 細胞毒殺試驗 8
四、 細胞週期分析 9
五、 細胞凋亡測定 9
六、 細胞自噬(autophagy)檢測 10
七、 Caspase活化分析 11
八、 西方點墨法 12
九、 統計分析 13
實驗結果 14
一、 評估dihydrosinularin對細胞毒殺效果 14
二、 Dihydrosinularin促使細胞週期停滯 14
三、 Dihydrosinularin誘導肺癌細胞株細胞凋亡 15
四、 Dihydrosinularin對細胞自噬之影響 16
五、 探討dihydrosinularin是否造成DNA損傷 17
討論 19
參考文獻 25

圖表目錄
表 1 西方點墨法使用抗體廠牌一覽表 29
圖 1 Dihydrosinularin結構及對肺癌細胞毒殺分析 30
圖 2 細胞型態表現 31
圖 3 Dihydrosinularin對細胞週期影響 33
圖 4 Dihydrosinularin與細胞週期調控蛋白表達關係 36
圖 5 Dihydrosinularin對細胞凋亡影響 37
圖 6 Dihydrosinularin對caspase-family活化之分析 40
圖 7 Dihydrosinularin對細胞凋亡調控蛋白表達關係 42
圖 8 評估dihydrosinularin對細胞自噬之影響 44
圖 9 Dihydrosinularin對DNA損傷蛋白表現之影響 46
圖 10評估dihydrosinularin 對粒線體的影響 47
圖 11 評估dihydrosinularin 對ROS的影響 48
圖 12 Dihydrosinularin誘導細胞死亡之路徑圖 49
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