作為常見的環境致癌物質，砷會對細胞造成許多有害的影響從而使細胞病變與癌化等等，然而近年也有研究發現砷的刺激能降低癌細胞的細胞遷移能力，進而降低癌症轉移的發生機率。本篇研究探討腫瘤抑制基因 p53 在砷降低癌細胞的細胞遷移能力中所扮演的角色及其影響的途徑。人類肺癌細胞 (A549) 在受到砷的刺激後會活化 p53 同時造成細胞遷移能力下降，當 p53 受到抑制時細胞遷移能力則會上升，砷刺激也同時活化能夠促進細胞遷移的 ERK 及 p38，且砷透過 ERK 促進細胞遷移相關的 AP-1-MMP-9 訊號傳遞路徑。然而，因砷刺激活化的 p53 會抑制 ERK，使 AP-1-MMP-9 途徑受抑制，最終造成砷刺激使細胞遷移能力下降。此外，當非小細胞肺癌細胞 (H1299) 細胞表達 p53 後也同樣透過抑制 ERK 及 p38 降低細胞的遷移能力。總結實驗結果，當 A549 受到砷的刺激後，活化的 p53會抑制 ERK，使後續的 AP-1-MMP-9 途徑作用受到抑制無法作用，最終造成細胞的遷移能力降低。本篇研究發現的砷對於癌細胞轉移的抑制效果以及所調控之訊號傳遞路徑，未來可以做為阻止癌症轉移與癌症治療的藥物標的研究方向。

As one of the common environmental carcinogens, arsenite not only causes many damages and stresses to the cell, but also leads to gene mutation and cancer. However, arsenite treatment was recently indicated to reduce the migratory ability of cancer cells and thus reduce the risk of cancer metastasis. In this study, we investigated the role of tumor suppressor gene p53 and the pathway that participated in arsenic-induced inhibiting cell migration in A549 cells. Arsenite treatment activates p53 and reduce cell migration, and once p53 is inhibited, cell migration will be increased. Arsenite treatment can also activate ERK and p38, which increase the ability of cell migration. ERK can regulate cell migration through AP-1/MMP-9 pathway. Arsenic-induced p53 inhibits ERK activation and lead to cell migration reduced. In addition, overexpressing p53 in H1299 cells by transfecting cells with plasmid carrying a WTp53 gene also reduce cell migration through ERK and p38 pathways. Our results reveal that arsenite treatment can activate p53, and thereby inhibit the ERK/AP-1/MMP-9 signaling pathway, resulting in reduced cell migration. Taken together, our study revealed the anti-migration ability of arsenite and targeting the arsenite-activated pathway may serve as a molecular approach to prevent cancer metastasis upon arsenite treatment.

目錄
中文摘要‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥2
英文摘要‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥3
緒論‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥4
材料與方法‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥13
結果‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥20
討論‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥26
參考資料‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥31
附圖‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥37

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