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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林淑萍 | |
| dc.contributor.author | Dai-Hua Tsai | en |
| dc.contributor.author | 蔡黛華 | zh_TW |
| dc.date.accessioned | 2021-05-19T18:04:26Z | - |
| dc.date.available | 2022-12-31 | |
| dc.date.available | 2021-05-19T18:04:26Z | - |
| dc.date.copyright | 2012-09-18 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-07-05 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/8050 | - |
| dc.description.abstract | Hepatocellular carcinoma (HCC) is the third cause of cancer-related death in the world. There is no efficient treatment for unresectable HCC. Sorafenib, a multiple kinase inhibitor, is the only targeted therapy drug for the treatment of unresectable HCC. It can improve the overall survival and progression time of the HCC patients. In clinical, lowering dosage is the solution to reduce sorafenib-induced side effects, like rash and hand-foot skin reaction. However, it leads to lower effectiveness of treatment. Low-dose sorafenib combined with other drugs (or adjuvant) to improve sorafenib efficacy may resolve the dilemma. In this study, Ganoderma triterpenoid T-612 from Lingzhi, a traditional Chinese medicine, was developed as an adjuvant of sorafenib for HCC. In HCC cell lines, compared to sorafenib alone, the combination with T-612 displayed synergistic cytotoxicity and growth inhibitory effects (IC50 of sorafenib was reduced 12 % to 51 %). Sorafenib treatment decreased colony formation efficiency, arrested cell growth in G0/G1 phase resulted by insufficiency of cyclin D, E and CDK2, increased reactive oxygen species, induced mitochondrial membrane damage and inhibited ERK phosphorylation. Apoptosis phenotypes, such as DNA fragmentation, caspase activation and AIF activation, were not detected whereas slight autophagy occurred by sorafenib treatment. However, autophagy is not the reason of cell death. Combined treatment with T-612 reinforced the effects of sorafenib, except ERK phosphorylation. The combination treatment induced serious autophagy, indicated by the increases of LC3-II and acidic vacule organells. Autophagy could be partially restored by autophagy inhibitor 3-MA. In conclusion, T-612 is a potential anti-cancer adjuvant that enhances the therapeutic efficacy of sorafenib in HCC cells. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-19T18:04:26Z (GMT). No. of bitstreams: 1 ntu-101-R99424012-1.pdf: 2098213 bytes, checksum: 6f0c3cb5c2915aa7bd5d1f7fe4d2e96f (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 摘要 I
Abstract II 英文名詞縮寫對照表 III 目錄 V 圖目錄 VII 1.研究背景 1 1.1.肝癌（Hepatocellular carcinoma） 1 1.2.肝癌的訊息傳遞與標靶治療 4 1.3.蕾莎瓦（Sorafenib） 5 1.4.靈芝（Ganoderma） 7 1.5.細胞週期（Cell cycle） 7 1.6.細胞程序性死亡（Programmed cell death） 9 2.研究目標 12 3.材料與方法 13 3.1.細胞培養 13 3.2.細胞活性測定 13 3.3.細胞膜通透性測定 13 3.4.胞落形成試驗 13 3.5.細胞週期分析 14 3.6.西方墨點法 14 3.7.細胞內粒線體活性氧化物（Reactive oxygen species，ROS）測定 15 3.8.細胞內粒線體膜完整性測定 15 3.9.細胞內Caspase活性測定 15 3.10.細胞內酸性囊狀胞器測定 15 3.11.統計分析 15 4.研究結果 16 4.1.T-612顯著地促進sorafenib對肝癌細胞株的抗癌活性 16 4.2.T-612促進sorafenib造成的細胞G0/G1時期停滯 18 4.3.T-612促進sorafenib造成的細胞活性氧化物累積及粒線體受損，移除活性氧化物無法恢復細胞活性，但可減緩粒線體受損情形 19 4.4.合併使用T-612無法增強sorafenib造成之訊息傳遞抑制 20 4.5.Sorafenib單獨處理或合併T-612皆不透過誘導細胞凋亡使細胞死亡 20 4.6.T-612增強sorafenib誘導之細胞自噬並使細胞死亡 20 5.討論 22 6.圖 26 7.參考文獻 37 8.附錄 42 附錄1.肝癌分期系統 42 附錄2.細胞自噬過程與其抑制劑 44 9.藥品材料清單 45 9.1.藥品與試劑 45 9.2.抗體 46 | |
| dc.language.iso | zh-TW | |
| dc.subject | 抗癌佐劑 | zh_TW |
| dc.subject | 靈芝三萜 | zh_TW |
| dc.subject | sorafenib | zh_TW |
| dc.subject | 肝癌 | zh_TW |
| dc.subject | 細胞週期停滯 | zh_TW |
| dc.subject | 細胞自噬 | zh_TW |
| dc.title | 靈芝三萜T-612透過誘導細胞自噬以促進Sorafenib於肝癌細胞株之效能 | zh_TW |
| dc.title | Ganoderma Triterpenoid T-612 Enhances Efficacy of Sorafenib in Hepatocellular Carcinoma Cell Line through Induction of Autophagy | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 楊雅倩,胡忠怡,張雅雯 | |
| dc.subject.keyword | 肝癌,sorafenib,靈芝三萜,抗癌佐劑,細胞週期停滯,細胞自噬, | zh_TW |
| dc.subject.keyword | hepatocellular carcinoma,sorafenib,Ganoderma,G0/G1 arrest,autophagy, | en |
| dc.relation.page | 46 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2012-07-06 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
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