記錄
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11837
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G0497866164
助教
查核
建檔完成
索書
號
查核完成
學校
名稱
輔仁大學
系所
名稱
營養科學系
舊系
所名
稱
學號
497866164
研究
林佩嬋
生(中)
研究
Pei Chan Lin
生(英)
論文
名稱
(中)
論文
名稱
(英)
葉酸缺乏活化 NF-κB 及 Hedgehog 訊息路徑促進肝癌細胞株 Hep3B 侵襲
性
Folate Deficiency Promotes Invasion of Hepatocellular Carcinoma Hep3B Cell
Mediated by Activated NF-κB and Hedgehog Signaling Pathway
其他
題名
指導
教授
(中)
許瑞芬
指導
教授
(英)
Rwei-Fen S. Huang
校內
全文
開放
日期
2016.9.1
校外
全文
2016.9.1
開放
日期
全文
不開
放理
由
電子
全文 同意
送交
國圖.
國圖
全文 2016.9.1
開放
日期.
檔案
說明
封面 中摘 英摘 致謝 縮寫表 目錄 圖目錄 第一章 前言 第二章 文獻回顧
第三章 實驗材料與方法 第四章 結果 第五章 討論 第六章 結論 圖表 參考
文獻
電子
全文
01 02 03 04 05 06 07 08 09 10 11 12 13 14 15
學位
類別
碩士
畢業
學年
度
99
出版
年
100
語文
別
中文
關鍵
葉酸缺乏 Hedgehog 傳訊 NF-κB 傳訊 肝癌細胞株
字(中)
關鍵
字(英)
摘要
(中)
本研究探討葉酸缺乏是否藉調節 NF-κB 與 Hedgehog (Hh) 訊息路徑之交
互作用促進肝癌細胞 Hep3B 侵犯性之影響。實驗選用肝癌細胞株 Hep3B
進行模式，實驗包含對照組、葉酸缺乏組及兩組分別加入脂多醣之誘發
組。結果顯示，葉酸缺乏與其誘發組皆增加 Hep3B 侵襲性。分別投予
PI3K/AKT，NF-κB 磷酸化及 Hh 傳訊抑制劑 (LY294002，Bay 及 KAADcyclopamine) 皆顯著降低葉酸缺乏所誘發之侵襲性。在 NF-κB 轉錄層次
方面，利用轉染方式將 NF-κB 載體送入 Hep3B，探討其轉錄層面表
現，發現在葉酸缺乏早期 NF-κB 轉錄活性增加，而投予 LY294002 及
Bay 皆顯著降低 NF-κB 報導基因活性，並顯性下降 NF-κB 及磷酸化
IκBα 之蛋白質表現。但投予抑制劑 KAAD-cyclopamine 並無抑制作
用。以即時定量 PCR 分析 Hh 相關基因表現，發現葉酸缺乏會導致
Shh，Ptch 及 Gli1 基因及 Shh 與 Gli1 蛋白質表現顯著增加，而抑制劑
LY294002，Bay 及 KAAD-cyclopamine 的給予，顯著抑制 Shh 及 Gli1 蛋白
質表現。而其表皮間葉轉換系統 (Epithelial-mesenchymal transition, EMT)
指標於基因層次有受到調控，上調 Snail，下調 E-cadherin 及 β-catenin 基
因與下調 E-cadherin 蛋白質表現，且(Matrix metalloproteinase; MMPs)
MMP2 及 MMP9 蛋白質及蛋白酶活性增加。分別投予抑制劑
(LY294002，Bay 及 KAAD-cyclopamine) 反轉葉酸缺乏對於 EMT 指標之影
響，且皆顯著降低葉酸缺乏所誘發之侵襲性 MMP2，MMP9 蛋白質及蛋
白酶活性。綜合上述，葉酸缺乏藉由活化 PI3k/AKT/NF-κB 路徑進而活
化 Hh 訊息傳遞路徑，改變 EMT 轉換系統，接續啟動轉移相關分子表
現，並促進肝癌細胞 Hep3B 之侵襲性。
摘要
(英)
論文
目次
目錄 頁碼 中文摘要 I 英文摘要 III 致謝 V 縮寫表 VII 圖目錄 XII 第一
章、前言 1 第二章、文獻回顧 3 一、肝癌侵犯性 3 二、表皮-間葉轉換系
統(Epithelial-mesenchymal transition，EMT) 與腫瘤移動、侵襲和轉移 5
三、啟動癌細胞轉移之分子機制 (一) Hedgehog (Hh)訊息傳遞路徑與腫瘤
生成之相關係 8 1. Hedgehog 訊息傳遞路徑 8 2. Hedgehog 訊息傳遞路徑失
調與腫瘤生成相關性 9 3. Hedgehog 訊息傳遞路徑在肝癌中的表現 10 4.
Hedgehog 訊息傳遞基因與腫瘤細胞侵襲、轉移的相關性 13 (二)
PI3K/AKT 與 NF-κB 訊息傳遞分子機制 17 1. PI3K/AKT 與 NF-κB 訊息
路徑影響癌細胞移動與侵犯之作用 機轉 18 (三) NFκB 與 Hedgehog 訊息
傳遞之交互作用 20 (四) 葉酸營養狀態對癌細胞移動及侵犯性之關係係
21 1. 葉酸營養狀態與癌細胞發展之關係 21 2. 葉酸營養狀態與發炎反應
對肝癌細胞侵犯之關係 22 (五) 研究假說與目標 24 第三章、實驗材料與
方法 25 一、實驗設計 25 二、實驗架構 27 三、實驗材料 28 四、實驗方
法 31 (一) 細胞培養 31 (二) 存活細胞計數 32 (三) 侵襲能能力分析測量 32
(四) 明膠酶譜法 33 (五) 反轉錄聚合酶連鎖反應 (Reverse transcription-PCR)
34 (六) 即時定量聚合酶連鎖反 應 36 (七) 西方墨點法 38 (八) 轉染及冷光
測定方法 40 五、統計分析 42 第四章、結果 43 一、葉酸缺乏及合併脂多
醣 ( LPS) 處理誘發 Hep3B 侵犯性之影響 43 二、PI3K，NF-κB 及
Hedgehog 訊息傳遞路徑參與葉酸缺乏誘發侵犯 性過程 44 三、葉酸缺乏
啟動 NF-κB 報導基因活性 45 四、葉酸缺乏啟動 Hedgehog 訊息傳遞路徑
相關分子表現 48 五、葉酸缺乏啟動 EMT 訊息傳遞路徑相關分子及基質
金屬蛋白酶 MMP2、MMP9 之表現 49 第五章、討論 51 一、葉酸缺乏藉
由改變上皮間葉系統 (EMT) 促進肝癌細胞株 Hep3B 侵犯性 51 二、葉酸
缺乏調控肝癌細胞 Hep3B 之 PI3K/AKT 及下游 NF-κB 訊息 傳遞分子表
現促進侵犯性 53 三、葉酸缺乏調控肝癌細胞 Hep3B 之 Hedgehog 訊息傳
遞分子表現 促進細胞侵犯性 57 四、葉酸缺乏調控 Hh 及 PI3K 訊息傳遞
分子交互作用 62 五、葉酸缺乏調控 Hh 及 NF-κB 訊息傳遞分子交互作
用 63 六、葉酸缺乏啟動 Hep3B 訊息傳遞相關分子機制 65 第六章、結論
67 參考文獻 85
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