陳進庭臺灣大學：口腔生物科學研究所白康俊Back, Hong-TsunHong-TsunBack2007-11-262018-07-092007-11-262018-07-092005http://ntur.lib.ntu.edu.tw//handle/246246/51300大部分的癌細胞依靠端粒酶（telomerase）來維持DNA端粒（telomere）的長度，而端粒長度的維持對於增生中的細胞是一個必要的條件。一般的體細胞當中並不會偵測到端粒酶的活性，所以抑制端粒酶的作用是一種治療癌症可以考慮的方法。BMVC【3,6-bis(1-methyl-4-vinylpyridium)carbazole 】設計可以與富含鳥糞嘌呤（Guanine rich）的四股結構（G-quadruplex）結合，尤其是人類的端粒序列5’-（TTAGGG）n-3’。本實驗目的在探討BMVC對細胞造成的毒性，以及立即性或後續的生物效應變化。實驗發現: (1)根據TRAP assay，隨著BMVC濃度的增加，端粒酶活性被抑制的情形也逐漸增強。(2) 經過BMVC處理的癌細胞端粒有縮短的現象。(3)MTT assay顯示，BMVC可以選擇性的傷害癌細胞且不會對正常細胞產生毒性。(4)目前研究發現BMVC是進入細胞核中而引起相關的生物效應變化。(5)在細胞的生長能力上，經BMVC處理的癌細胞生長速度有明顯的減慢。Compare to normal somatic cells, more than 85% of cancer cells have higher telomerase activity to maintain their length of telomere. Therefore, inhibiting the function of telomerase is a considerable way to interfere cancer proliferation. BMVC was designed for interacting with G-quadruplex, a DNA four strand structure that is abounded with Guanine nucleotides, especially the sequence of human telomere [5’-（TTAGGG）n-3’]. Based on acute cytotoxicity assay, BMVC has higher cytotoxicity on cancer cells, which 50% lethal dose is about 10 μM. According to telomeric repeat amplification protocol assay, BMVC is a potent telomerase inhibitor with 50% inhibition concentration at 0.25 μM. Under confocal microscopy observation, BMVC enter the nucleus which might further affect cellular function. Cell culture and animal study show that proliferation ability of cancer cells may inhibited under nonacute cytotoxic concentration of BMVC treatment.縮寫表……………………………………………………….2 英文摘要…………………………………………………….3 中文摘要…………………………………………………….4 序論………………………………………………………….5 研究目的…………………………………………………...12 實驗材料…………………………………………………...13 實驗方法…………………………………………………...15 結果……………………………………………………...…25 第一部份…………………………………………………...25 第二部份……………………………………………...……27 第三部份………………………………………………..….30 第四部份……………………………………………..…….32 第五部份…………………………………………..……….35 討論……………………………………………..………….37 圖表……………………………………………………...…42 附圖………………………………………………………...69 參考文獻…………………………………………………...78en-US鳥糞嘌呤四股結構G-quadruplex binding compound[SDGs]SDG3other