蘋果多酚抑制轉錄因子Snail調控Focal adhesion kinase基因表現之抗腸癌轉移作用

Apple polyphenol inhibits colon carcinoma metastasis via targeting snail binding to focal adhesion kinase

洪嘉鴻(Chia-Hung Hung)

指導教授 ： 王朝鐘

中山醫學大學/醫學院/生化暨生物科技研究所/博士(2015年)

摘要

根據文獻的報導蘋果多酚在多種癌症上具有抗腫瘤的活性，但是蘋果多酚對於是否能夠影響腸癌腫瘤轉移尚未釐清。因此在本實驗當中欲探討蘋果多酚是否對腸癌細胞轉移具有抑制的效果。本實驗結果顯示蘋果多酚對於腸癌細胞的存活率、細胞增殖與細胞週期分佈並沒有顯著性的差異，但是蘋果多酚卻能有效的抑制腸癌細胞移動、癌細胞侵犯、非固著性依賴生長及癌細胞黏附的特性。另外，蘋果多酚也會降低細胞骨架生成影響細胞骨架的結構。進一步發現蘋果多酚並不會影響Talin、actinin以及vinculin等蛋白，但可以抑制細胞黏附分子FAK蛋白表現而影響下游訊號傳遞蛋白如paxillin、Src、PI3K 以及 Akt等。此外，我們也發現到蘋果多酚並沒有影響FAK所調控的下游細胞骨架相關蛋白分子Rac-1、Cdc42、Rho A的總蛋白表現而是抑制其蛋白活性。實驗結果也證明蘋果多酚抑制FAK的表現是發生在轉錄作用，經由蘋果多酚影響轉錄因子Snail結合到FAK啟動子的序列，降低其結合的能力而影響下游的訊息傳遞。利用轉殖Flag-Snail表達系統顯示在蘋果多酚處理下FAK下游傳遞訊息是可以回復的。利用異體腫瘤移植模式，結果顯示蘋果多酚可以遏止腸癌腫瘤發生與轉移能力。綜合實驗結果，我們首先發現蘋果多酚影響轉錄因子Snail結合到FAK啟動子序列進而影響下游傳遞訊息抑制腸癌腫瘤移動與侵犯能力。

關鍵字

腸癌 ； 轉移 ； 蘋果多酚

並列摘要

Apple polyphenon (AP) has been reported to possess potent anti-tumor activity on several carcinomas, but the effects of AP on colon cacner with emphasis on metastatic capability is not clarified. Herein, we aimed to investigate inhibitory effects of AP on colon cancer cells. Our results revealed that AP treatments insignificantly affected cell viability, proliferation and cell cycle distribution of colon cancer cells DLD-1 but suppressed migration, invasion, colony formation and adhesion of the cell. In addition, AP reduced expression of cytoskeletal protein tubulin and F-actin, and consequently altered the cytoskeleton structure. Interestingly, we found that AP treatments reduced expression of focal adhesion kinase (FAK) but not Talin,

並列關鍵字

colon cancer ； metastasis ； apple polyphenol

參考文獻

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