臺灣博碩士論文加值系統

Doxorubicin (DXR)及5-fluorouracil (5-FU) 是臨床上常用來治療癌症的化療藥物，但是由於它們的效果不佳或產生的抗藥性而降低癌症治療的成功率。所以目前亟需的是研發新的治療方式，可能透過結合不同種類的藥物或其他途徑來克服這些治療上的困難並提升效果。有許多研究已經指出，去甲基斑蝥素 (Norcantharidin, NCTD) 在細胞中可藉由細胞分裂時的有絲分裂停止或造成誘導細胞產生凋亡的途徑，達到對抗腫瘤生長的效果。因此本篇研究試著利用NCTD在細胞內所造成的一些反應，結合目前所使用的抗癌藥物DXR或5-FU，去分析兩種藥物的結合是否對CT-26小鼠直腸癌腫瘤細胞有更好的毒殺效果以及一些相關機制的探討。我們的結果顯示NCTD同時處理DXR或5-FU有著不同的反應。根據細胞存活率以及細胞凋亡之分析，我們發現NCTD可增強DXR或5-FU抑制CT-26細胞生長或誘導凋亡的能力。其中DXR的反應，我們利用luciferase報導基因的分析以及西方墨點法的測試，看到了DXR與NCTD可透過降低NF-□B的活性以及抑制GST-π蛋白質的表現來達到抑制腫瘤生長的效果。然而，DXR與NCTD同時作用時所產生的抗腫瘤活性，可能不是透過 mitogen activated protein kinase (MAP kinase) 或 sonic hedgehog (shh) 這兩組訊息傳遞路徑所達成。此外，當5-FU與NCTD同時作用時，利用反轉錄聚合&;#37238;鏈鎖反應發現，兩者可加乘性降低thymidylate synthase (TS) mRNA的表現量。但是NCTD與5-FU兩者結合時的效果並不是透過NF-kB以及shh路徑的調控，其中的相關機制可能是透過MAP kinase 路徑中磷酸化-JNK的訊息傳遞所引發的。最後的總結是NCTD可透過誘導細胞凋亡以及減低藥物抗藥性，來提升化學治療藥物DXR及5-FU的療效。因此，進一步釐清NCTD在輔助化療的作用機轉，將有助於作為提升抗腫瘤治療的新策略。

目錄
中文摘要……………………………………………………….1
英文摘要……………………………………………………….2
I. 前言
1.大腸癌..............……………………………………......5
2.化學治療…………………...………………………….6
3.抗藥性蛋白……………………………….…………...9
4.轉錄因子與NF-□B……………………………………12
5. 去甲基斑蝥素……………………………………….14
II. 目的……………………………………………………..16
III. 材料與方法
1.儀器…………………………………………………..17
2.材料…………………………………………………..18
3.實驗方法……………………………………………..23
IV. 結果……………………………………………………..30
V. 討論……………………………………………………..36
VI. 總結……………………………………………………..41
VII. 參考文獻………………………………………………..43
VIII. 圖表……………………………………………………..52
IX. 附錄……………………………………………………..66

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