楊泮池2006-07-262018-07-112006-07-262018-07-112004http://ntur.lib.ntu.edu.tw//handle/246246/23654肺癌佔目前所有癌症的12.8%, 並且佔所有癌症死因的17.8%. 就台灣而言, 肺癌也是主要的癌症死因. 每年約有6000 人死於肺癌, 顯示了新而有效的療法 之重要性.研究顯示使用外加抑制劑來抑制端粒脢的活性會造成差異相當大的結 果, 包括細胞的立即死亡, 到經過一段時間後細胞生長變慢, 到細胞生長不受影 響. 端粒脢的抑制是否可以作為人類癌症治療的一個模式仍不十分清楚.第一年 的研究中, 我們已使用2'-O-Methyl RNA, 透過抑制端粒脢的作用, 來達到抑制 肺癌細胞生長的效果. 含有人類端粒脢RNA 模板互補序列的2'-O-Methyl RNA 利用陽離子性微脂體作為載體來轉殖進入一相當惡性之肺癌細胞株,CL1-5. 轉 殖後的細胞與對照組比較起來,細胞生長受到明顯的抑制. 而這些轉殖後的細胞 的端粒脢活性有降低的情形, 細胞凋亡的比例也增加。在本年度, 我們使用同樣 的轉殖模式來應用到不同的肺癌細胞株, A549 上. 我們發現, 轉殖後的細胞與對 照組比較起來,細胞生長受到明顯的抑制. 細胞凋亡的比例也增加. 但轉殖後的 細胞的端粒脢活性降低的情形並不顯著. 在下年度, 我們將研究轉殖後的細胞的 下游基因表現及侵襲能力的變化.Lung cancer is the cause of 12.8% of malignancy and leads to 17.8% of cancer deaths worldwide. Lung cancer is also the leading cause of cancer death in Taiwan. Annually, there were 6000 patients died of lung cancer in Taiwan, emphasizing the need for new and effective treatment. Studies of the inhibition results by exogenously added inhibitors have produced contradictory results, ranging from immediate cell death, to decreased cell proliferation after a long delay, to no change in proliferation. The potential of telomerase inhibition as a therapeutic modality for human cancer remains unknown. In the first year of this proposed project, we used 2'-O-methyl RNA for cell growth arrest of lung cancer through telomerase inhibition. 2'-O-methyl RNA with complementary human telomerase RNA sequence was transfected into a cultured lung cancer cells, CL1-5, using cationic liposome as a vector. The cell growth was inhibited by the 2'-O-methyl RNA in comparison with the control groups. The 2'-O-methyl RNA transfected cells showed decreased telomerase activity and increased proportion of apoptotic cells. In the second year, we applied the same methodology to another lung cancer cell lines, A549. The cell growth of A549 cells was inhibited by the 2'-O-methyl RNA in comparison with the control groups. The 2'-O-methyl RNA transfected cells showed little decreased telomerase activity and increased proportion of apoptotic cells. Next year, we will study the downstream gene expression profile and invasion ability change of the 2'-O-methyl RNA transfected cells.application/pdf45327 bytesapplication/pdfzh-TW國立臺灣大學醫學院內科基因治療肺癌2-O-Methyl 核糖核酸Lung cancergene therapy2-O-Methyl RNA[SDGs]SDG3reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/23654/1/922314B002221.pdf