臺灣博碩士論文加值系統

Cisplatin被廣泛運用在各種癌症的治療，例如肺癌。做為臨床第一線的抗癌藥物，它可以透過與DNA的交互作用造成DNA損傷並產生大量ROS進而造成細胞死亡。然而，該治療因為抗藥性和劑量毒性產生使用上的限制性。因此，在臨床試驗上有許多藥物嘗試與cisplatin合併使用來克服這些問題。其中的一種藥物為buthionine-sulfoximine (BSO)，它是Glutathione (GSH) 的抑制劑，在先前實研究已被證實，BSO能增加細胞內的ROS。

Cisplatin is wildly used for the treatment of lung cancer. It can cause cell death mediated by triggering DNA damage and reactive oxygen species (ROS). However, the treatment has its limitation due to its side effects and dose-limiting toxicity. Therefore, many drugs have been explored in combination with cisplatin to overcome these limitations in clinical trials. One of the drugs used to combination of cisplatin is buthionine-sulfoximine (BSO), a glutathione inhibitor. Previously, we showed that BSO treatment increased intracellular ROS.

目錄

Abstract i
中文摘要 ii
目錄 iii
圖目錄 iv
緒論 1
Cisplatin 1
活性氧化物 (Reactive Oxygen Species, ROS) 2
Glutathione 2
Buthionine-sulfoximine (BSO) 以及N-acetyl-L-cysteine (NAC) 3
γ-H2AX與DNA雙股斷裂修補 4
PI3K/AKT訊息傳遞路徑 5
研究動機與目標 6
實驗材料 7
實驗方法 11
實驗結果 18
一、cisplatin配合BSO處理下，造成細胞的生存率下降，γ-H2AX 和cleaved caspase 3的表現量增加 18
二、cisplatin配合BSO處理A549細胞，會延遲細胞進行同源重組的DNA修復機制 19
三、NAC會抑制cisplatin造成的細胞死亡，使γ-H2AX與cleaved caspase 3 蛋白表現量下降 19
四、cisplatin配合BSO處理A549肺癌細胞，γ-H2AX螢光表現會增加 20
五、cisplatin配合NAC處理A549肺癌細胞，γ-H2AX螢光表現會被抑制 20
六、BSO會增加cisplatin造成的DNA受損程度 20
七、NAC會降低cisplatin造成的DNA受損程度 21
八、cisplatin配合BSO作用下會降低長期的細胞增殖能力，NAC可以回復cisplatin造成的細胞死亡 21
九、cisplatin配合BSO處理A549肺癌細胞，pAkt的蛋白表現會增加 22
實驗討論 23
實驗圖表 26
參考文獻 35
附圖 40
附錄 43

圖目錄

圖 一、 cisplatin配合BSO處理下，會造成A549細胞的生存率下降，γ-H2AX 和cleaved caspase 3的表現量增加。 26
圖 二、cisplatin配合BSO處理A549細胞，會延遲細胞進行同源重組的DNA修復機制。 27
圖 三、 NAC會抑制cisplatin造成的細胞死亡，使γ-H2AX 和cleaved caspase 3表現量下降。 28
圖 四、BSO會增加cisplatin在A549細胞中誘導的γ-H2AX螢光表現量。 29
圖 五、NAC會抑制cisplatin在A549細胞中誘導的γ-H2AX螢光表現量。 30
圖 六、BSO會增加cisplatin在A549細胞中造成的DNA受損。 31
圖 七、NAC會降低cisplatin在A549細胞中造成的DNA受損。 32
圖 八、BSO或NAC對於低劑量的cisplatin在A549細胞中造成的細胞生存率之影響。 33
圖 九、cisplatin配合BSO處理下，磷酸化Akt的表現量會增加。 34

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