臺灣博碩士論文加值系統

肺癌細胞的上皮間質轉化是癌細胞獲得侵襲移動能力的先決條件，隨後癌細胞才能進行轉移。在本研究中，我們使用不同有機溶液來萃取覆盆子，分別獲不同萃取物：甲醇萃取物(RIME)、氯仿萃取物(RICE)、乙酸乙酯萃取物(RIEE)、正丁醇萃取物(RIBE)、水萃取物(RIWE)。研究結果顯示，RIEE具有多種多酚類成分，包括gallic acid、 protocatechuic acid、epigallocatechin、methyl gallate、epicathchin、epigallocatechin gallate、rutin、epicatechin-3-gallate 和naringin。使用RIEE來處理高轉移人類肺癌A549細胞株，具有顯著的抑制invasive、motility、 spreading和migratory能力。Zymography以及promoter luciferase分析顯示，RIEE可以抑制MMP-2及u-PA表現和轉錄活性。分子分析可以觀察到RIEE會增加A549細胞膜上E-cadherin的濃度，這可當作細胞型態朝上皮細胞特徵轉變的反應。同時，RIEE也可以上調上皮細胞標記，如α-catenin以及降低間質細胞標記，如snail-1和N-cadherin，促進癌細胞的侵襲和轉移。RIEE也抑制NF-κB和p-Akt蛋白的表現。從我們的結果顯示，RIEE的抗侵襲/抗腫瘤效果與相關機轉證實，RIEE值得再進行臨床相關模式測試，來探討其對抗轉移性肺癌細胞的潛在益處。

The epithelial-to-mesenchymal transition (EMT) in lung cancer cells is considered pre-requisite for acquiring invasive/migratory phenotype, and subsequent metastasis. In the present study, we extracted raspberry Rubus idaeus L. with methanol (RIME), chloroform (RICE), ethyl acetate (RIEE), n-butanol (RIBE), and water (RIWE). Our results showed that RIEE, which contained polyphenols including gallic acid, protocatechuic acid, epigallocatechin, methyl gallate, epicathchin, epigallocatechin gallate, rutin, epicatechin-3-gallate, and naringin, treatment significantly inhibits invasive, motility, spreading, and migratory potential of highly metastatic human lung cancer A549 cells. Zymography and promoter luciferase analysis revealed that RIEE inhibits the proteinase and transcription activities of MMP-2 and u-PA, respectively. Molecular analyses showed that RIEE increases E-cadherin level that was localized mainly at cellular membrane as evidenced by confocal analyses in A549 cells, which might be responsible for morphologically observed shift towards epithelial character. RIEE also induced up-regulation of epithelial marker such as α-catenin and decreased the mesenchymal markers such as snail-1 and N-cadherin, which promote call invasion and metastasis. RIEE also inhibited NF-κB and p-Akt protein expression. Together, our results showing anti-invasive/anti-tumor effects of RIEE and associated mechanisms suggest that RIEE should be tested further in clinically relevant models towards exploiting its potential benefits against metastatic lung cancer cell.

目錄…………………………………………………………I
中英文摘要…………………………………………………II
縮寫表………………………………………………………IV
壹、緒論…………………………………………………… 1
貳、研究動機………………………………………………17
參、實驗材料與方法………………………………………18
肆、實驗結果………………………………………………34
伍、討論……………………………………………………40
陸、參考文獻………………………………………………45
柒、圖表與圖表說明………………………………………55

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