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標題: | 血根鹼與TRAIL引起人類口腔癌細胞株細胞凋亡加成作用之研究 Sanguinarine sensitizes human oral cancer cells to TRAIL-induced apoptosis |
作者: | Shim-Jie Lin 林世杰 |
指導教授: | 郭彥彬(Mark Yen-Ping Kuo) |
關鍵字: | 口腔癌,血根鹼,TRAIL,細胞凋亡, oral cancer,sanguinarine,TRAIL,apoptosis, |
出版年 : | 2011 |
學位: | 碩士 |
摘要: | 在台灣,口腔癌為一常見癌症,且發生率和死亡率都不斷攀升,根據衛生署統計,口腔癌自1991年起至今,一直都為癌症十大死因之一。近年來,雖然整體醫療技術不斷進步,但口腔癌病人之五年存活率未有顯著改善。因此,迫切需要新的口腔癌診斷與治療的方法,來改善病人的存活率與生活品質。近幾年研究指出,血根鹼(sanguinarine)可抑制胰腺癌、攝護腺癌、皮膚表皮癌及大腸癌細胞生長或產生細胞凋亡。因此本研究以人類口腔癌細胞株SAS及Ca9-22來探討血根鹼對口腔癌細胞的影響,並進一步了解其可能的機制及血根鹼是否可當作口腔癌抗癌藥物。結果顯示,以sanguinarine處理SAS及Ca9-22 細胞,可以明顯抑制細胞生長,且濃度愈高或作用時間愈長,抑制效應就愈明顯 (SAS與Ca9-22 之IC50 分別為1.1 μM及1.2 μM )。西方墨點分析顯示血根鹼增加SAS與Ca9-22細胞中DR4,DR5與 t-bid蛋白質量的表現,進而活化pro-caspase-8與pro-caspase-9,表示血根鹼主要經由活化外生性細胞凋亡路徑,然後誘發內生性細胞凋亡路徑產生細胞凋亡。更進一步發現在SAS與Ca9-22細胞中加入自由基(ROS)的抑制劑,N-acetylcysteine(NAC)後可降低sanguinarine所誘發的細胞凋亡反應,顯示ROS在sanguinarine引起的人類口腔癌細胞細胞凋亡中扮演了重要的角色。 西方墨點法分析發現NAC可降低SAS與Ca9-22細胞中DR4和DR5 蛋白量的表現,可能因此降低sanguinarine所誘發的細胞凋亡 。
低毒性濃度(SAS處理0.55μM和Ca9-22處理0.6μM)的血根鹼協同5ng/ml的TRAIL對口腔癌細胞細胞凋亡有加乘的效果。對於血根鹼是否可當作口腔癌抗癌藥物則需要再以更精確的動物實驗及臨床試驗作更深入的評估其抗癌的功效。 Oral cancer has been one of the top ten leading causes of death from cancer since 1991 in Taiwan. Despite significant advance in cancer treatment, the overall five-year survival for patients of oral cancer is still lowest among major cancers. As traditional treatments fail to cure oral cancer, urgent demand for efficient chemotherapeutic agents to improve survival and quality of life has motivated this study. Sanguinarine has been shown to selectively induce tumor apoptosis in several types of cancers and is regarded as a promising chemotherapeutic agent. In this study, we showed that sanguinarine significantly suppressed the growth of oral cancer SAS and Ca9-22 cells in the time-dependent and dose-dependent manner. Western blotting revealed that sanguinarine induced apoptosis in these cells and showed sanguinarine increased DR4, DR5 protein expression and activated caspase-8 and -9. Subtoxic concentrations of sanguinarine sensitize two TRAIL resistant human oral cancer cells. The apoptosis induced by the combined treatment of TRAIL and sanguinarine was mainly achieved through activation of DR5/TRAIL and DR4/TRAIL apoptotic pathways.Combined treatment of sanguinarine and TRAIL may be used as a new promising therapy for oral cancer. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/24120 |
全文授權: | 未授權 |
顯示於系所單位: | 口腔生物科學研究所 |
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