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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 郭彥彬(Yen-Ping Kuo),蕭宏昇(Michael Hsiao) | |
| dc.contributor.author | Geng-Nan Chiang | en |
| dc.contributor.author | 江耿男 | zh_TW |
| dc.date.accessioned | 2021-06-08T05:14:37Z | - |
| dc.date.copyright | 2006-08-03 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-06-29 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/24038 | - |
| dc.description.abstract | 魚藤素(deguelin)是一種非常具有發展潛力，可以抵抗癌症細胞生長的天然合成藥物。其主要機制在於抑制細胞AKT 蛋白的活性，在許多癌細胞種類中已經被證明AKT 蛋白都有過度活化的情況，如支氣管上皮細胞癌、結腸癌、急性骨髓白血病(acute myeloid leukemia，AML)、非小細胞肺癌(NSCLC)、乳癌以及皮膚鱗狀細胞(cutaneous squamous cell)，在使用魚藤素治療後具有很好的抑
癌功效。但是在口腔癌治療研究中則未被證實有任何功能以及在口腔癌中p-AKT抑制劑deguelin 如何影響細胞增生。我們在臨床檢體中發現，p-AKT 的過度表現與口腔癌形成可能具有密切的關聯。本研究擬探討透過藥物處理抑制PI3K/AKT 路徑是否影響口腔癌細胞增生，我們使用deguelin 處理口腔癌細胞株，觀察細胞株的生長曲線改變、細胞凋亡、對於細胞株侵入或平移的影響，以及基因蛋白的表現有何改變。我們發現，在加入deguelin 後，口腔癌細胞株SAS 及 Cal27 生長速度會變得較緩慢，經由西方墨點法發現，其內生性的AKT 活性會被deguelin 抑制。細胞轉移分為入侵與平移，我們用boyden chamber 來偵測細胞的入侵能力，利用wound colonization 來估計細胞的平移能力。而結果顯示deguelin 對於細胞株SCC4 與HSC3 的平移能力也有抑制的效果，對於細胞株ca922 與SAS 侵入能力也有明顯的抑制。在藥物加成作用的實驗中，我們發現如果使用低劑量的cisplatin 與degelin 一起作用，會引起細胞凋亡的數目增多，使細胞提高藥物敏感性。因此，我們認為deguelin 可以有效的抑制口腔癌細胞AKT 的活化，造成口腔癌細胞生長趨緩，轉移能力下降，與藥物cisplatin 一起治療口腔癌可以增加細胞 cisplatin 的敏感性，降低藥物的使用劑量。 | zh_TW |
| dc.description.abstract | Deguelin is a very potential, natural plant-derived drug which can suppress cancer cell growth. The mechanism is to suppress the activity of p-AKT, which is proven to over express in many cancer cell types, as human bronchial epithelial (HBE), colon cancer, acute myeloid leukemia (AML), NSCLC, breast cancer and cutaneous squamous cell. After treating deguelin, it gets good efficacy in suppressing cancer cells. But the function of deguelin is not proven in oral cancer therapy research, and how deguelin, AKT inhibitor, suppresses the amplification of oral cancer. We found it had high correlation with over-expression and oral cancer formation in clinical oral cancer tumor sample. In this study, we determined whether inhibition of PI3K/AKT pathway through pharmacological manipulation enhance inhibiting growth of oral cancer. We used deguelin to treat oral cancer cells and observed whether it changed cell growth rate, resulted in cell apoptosis, influenced cell migration and invasion, and changed gene expression in oral cancer. We found that the growth rate of SAS and Cal27 were decreased after treating them with deguelin. The western blot data showed that endogenous AKT activity was suppressed by deguelin. We used boyden chamber to determine cell invasion potentials and used wound colonization to determine cell migration ability. Our data showed that deguelin could decrease HSC3 and SCC4 migration ability, and it also reduced CA922
and SAS invasion potentials. Furthermore, in synergistic effect experiment, low dose of deguelin and cisplatin enhanced more cell apoptosis and drug sensitivity. We thought deguelin maybe a candidate drug of oral cancer therapy by reducing cell growth rate, invasion potentials and migration ability. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T05:14:37Z (GMT). No. of bitstreams: 1 ntu-95-R93450006-1.pdf: 4898312 bytes, checksum: d4e5895132c2bfe20366fdc96c6fa622 (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 中文摘要.............................................1
Abstract.............................................2 前言 研究緣起.............................................4 口腔癌分類...........................................8 文獻探討 PI3K/AKT 簡介........................................9 Rotenone 和Deguelin 的簡介..........................15 特別目標............................................18 實驗材料與方法......................................19 實驗結果............................................28 實驗討論............................................71 未來展望............................................78 參考文獻............................................83 附錄................................................94 | |
| dc.language.iso | zh-TW | |
| dc.subject | 口腔癌 | zh_TW |
| dc.subject | 魚藤素 | zh_TW |
| dc.subject | oral cancer | en |
| dc.subject | deguelin | en |
| dc.subject | PI3K/AKT | en |
| dc.title | 以藥物魚藤素(Deguelin)抑制PI3K/AKT 之活性來治療口腔癌 | zh_TW |
| dc.title | Pharmacological inhibition of PI3K/AKT activity by deguelin to treat oral cancers | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 郭生興 | |
| dc.subject.keyword | 魚藤素,口腔癌, | zh_TW |
| dc.subject.keyword | deguelin,oral cancer,PI3K/AKT, | en |
| dc.relation.page | 103 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2006-06-30 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 口腔生物科學研究所 | zh_TW |
| 顯示於系所單位： | 口腔生物科學研究所 | |
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