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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳信銘(Hsin-Ming Chen) | |
| dc.contributor.author | Shih-Feng Tseng | en |
| dc.contributor.author | 曾士峰 | zh_TW |
| dc.date.accessioned | 2021-06-13T01:13:11Z | - |
| dc.date.available | 2016-10-03 | |
| dc.date.copyright | 2011-10-03 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-03 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/29641 | - |
| dc.description.abstract | 根據行政院衛生署民國98年統計資料，口腔癌已經成為台灣男性十大癌症死亡率的第四位，並且還未有趨緩的現象。同時，近年來雖然口腔研癌的治療方法有很大的進步，但是因為手術造成的顏面缺損，常使病人因之卻步而延誤治療時機，因此尋求更好的口腔癌治療方法是非常迫切需求的。
5-氨基酮戊酸光動力治療(5-aminolevulinic Acid-Photodynamic Therapy；ALA-PDT)是一個新興的癌症治療方式。先前我們實驗室不論在基礎或臨床試驗上，都發現ALA-PDT對於口腔癌及癌前病變都有不錯的治療效果。但根據我們先前研究結果發現病人腫瘤的特性、位置、大小及深度等都會影響ALA-PDT治療口腔癌的效果；另外ALA-PDT在口腔癌治療上所需時間較長、次數較多，並且費用較高，因此尋求一個毒性較低且可以有效增強ALA-PDT效果的藥物是有必要的。 我們利用Ca9-22以及SAS兩株口腔癌細胞株進行MTT assay細胞存活實驗發現，若先使用薑黃素(Curcumin)處理細胞後，再施與ALA-PDT的治療，薑黃素會明顯增加ALA-PDT殺死細胞的能力；且隨著薑黃素劑量的提高，除了會繼續增加ALA-PDT殺死細胞的能力外，另一方面也可以降低ALA-PDT殺死原相同數目細胞所需之照射焦耳數。 在Tunel Assay染色發現，先以薑黃素處理的ALA-PDT會增加DNA fragmentation，並且由西方點墨法(Western-blot)發現，此方式會增加PARP cleavage form、Caspase-8及Caspase-9蛋白表現。在細胞凋亡路徑的加乘性分析中，增加內生性細胞凋亡路徑(Intrinsic apoptotic pathway)是經由促進Cytochrome-C釋出、bid切割、Bcl-2抑制及Caspase-9活化所造成。這些結果說明加乘性的細胞毒殺效果主要是透過第一型細胞死亡( Type I Cell Death )-細胞凋亡(Apoptosis)。 我們進一步利用螢光光譜儀探討上述研究細胞凋亡現象增強的原因發現，先以薑黃素處理口腔癌細胞後，會使吸收波長為635+5nm的光感物質Protoporphyrin IX(PpIX)螢光強度增強。這個表現代表PpIX生成量的增加，這可能是增加細胞毒殺效果的原因之一。 此外，我們先以薑黃素處理Ca9-22口腔癌細胞株後再進行ALA-PDT發現，細胞自噬( Autophagy )的指標蛋白LC3-II的表現會增加。再以細胞自噬抑制劑3-Methyladenine (3-MA)處理，則細胞的存活率會增加。這個研究結果說明，先以薑黃素處理再進行ALA-PDT也會增加第二型的細胞死亡( Type II Cell Death )-細胞自噬，來增加細胞的毒殺效果。 由本研究結果可知，先以短時間且毒性較低的薑黃素處理，可以明顯增加PpIX的生成；進而增加ALA-PDT細胞凋亡和細胞自噬而增加細胞的死亡。此外，合併使用薑黃素可縮短ALA-PDT的照射時間，而不減ALA-PDT治療口腔癌的效果。 | zh_TW |
| dc.description.abstract | According to the latest statistics from the Department of Health, oral cancer has been the fourth leading cause of cancer death in males in Taiwan, and the mortality rate hasn’t been slowed down. Recently, there are many new strategy to treat oral cancer, but facial defect resulting from surgery made the patient hesitate to get early treatment. Therefore, finding a better treatment for oral cancer treatment is urgent.
5-Aminolevulinic acid (ALA) is a novel photosensitizer for photodynamic therapy (ALA-PDT). Our previous studies showed ALA-PDT could induce cytotoxicity in oral cancer cells. It can also treat potentially malignant disorders. However, oral cancers with different sizes, sites, invasion depthes and characteristics could result in different efficiency in ALA-PDT. On the other hand, it takes much time and high costs during ALA-PDT. Therefore, finding a drug with low toxicity and high efficiency to enhance the ALA-PDT is necessary. In our our results, oral cancer cell lines such as Ca9-22 and SAS pretreated with curcumin and then treated with ALA-PDT exhibited dose-dependent cytotoxicity. In addition, combination therapy could lead to DNA fragmentation detected by the Tunel assay, and effectively induced apoptotic cell death by Western-blotting. Upregulated PARP, enhanced Cytochrome-C release, downregulated Bcl-2, Bid, and an increase in the ratio of pro-apoptotic/anti-apoptotic protein, which were associated with an increase in caspase activity. We also found that combination therapy could enhance accumulation of protoporphyrin IX (PpIX) and result in an increased the cytotoxic effect on oral cancer cells. Furthermore, we found that the marker of autophagy, LC3-II level was increased upon preatreatment of Ca9-22 cells with curcumin; treatment with autophagy inhibitor, 3-Methyladenine (3-MA) increased the cancer cell survival. It suggests that combination therapy could also induce autophagic cell death to cause cancer cell death. In conclusion, these data suggested that curcumin is a potential drug that can be used for ALA-PDT pretreatment. It effectively induces PpIX accumulation, cell apoptosis, autophagic cell death, and increase ALA-PDT efficacy on treatment of oral cancer cells. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T01:13:11Z (GMT). No. of bitstreams: 1 ntu-100-R98450010-1.pdf: 2624265 bytes, checksum: 82d5c5e6372c73e225225b150dd304e8 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 口試委員會審定書……………………………………………………………………..I
致謝………………………………………………………………………………….....II 中文摘要………..……………………………………………………………...……...III 英文摘要(Abstract) ……..…..……..…………..……………………………………..V 目錄(Index)...…………………………….……………………….................................1 第一章 導論(Introduction) 第一節 口腔癌 1.1-1、口腔癌簡介...................................................................................................3 1.1-2、口腔癌診斷...................................................................................................4 1.1-3、口腔癌治療與預後.......................................................................................5 第二節 光動力治療 1.2-1、光動力治療源起..........................................................................................6 1.2-2、光動力治療基本原理..................................................................................7 1.2-3、5-氨基酮戊酸光動力治療(ALA-PDT).......................................................8 第三節 薑黃素..........................................................................................................10 第四節 細胞死亡機制 1.4-1、細胞死亡方式.............................................................................................11 1.4-2、細胞凋亡(Apoptosis)..................................................................................11 1.4-3、細胞自噬(Autophagy)………....................................................................15 第五節 癌症合併治療(Combination therapy)….....................................................17 第六節 實驗目的.....................................................................................................18 第二章 實驗材料與方法(Material and Method) 第一節 細胞來源與培養..........................................................................................19 第二節 薑黃素合併5-氨基酮戊酸光動力治療方法 2.2-1、光動力機器.................................................................................................19 2.2-2、細胞處理.....................................................................................................20 第三節 PpIX螢光測定............................................................................................21 第四節 細胞存活率試驗(MTT assay) ....................................................................21 第五節 西方點墨法(Western-blot) 2.5-1、蛋白質萃取.................................................................................................21 2.5-2、蛋白質濃度測定(Bicinchoninic Acid Protein Assay)................................22 2.5-3、膠體電泳(SDS-PAGE)…………………………………………………..23 2.5-4、蛋白質轉漬………………….……………………………………………23 2.5-5、壓片/顯影呈色……………………………………………………………23 第六節 抑制劑處理…………………………………….………….............................24 第七節 Tunel assay…………………………………………………………………...24 第三章 實驗結果(Results) 第一節 ALA-PDT抑制Ca9-22及SAS細胞存活...................................................26 第二節ALA-PDT與不同劑量薑黃素作用會明顯增加ALA-PDT對Ca9-22及SAS細胞毒殺效果....................................................................................................26 第三節ALA-PDT照射強度增加與薑黃素作用會明顯增加Ca9-22及SAS細胞毒殺效果…………………………………………………………………………....27 第四節 ALA-PDT與薑黃素作用會增加apoptosis的發生....................................27 第五節 ALA-PDT與薑黃素作用在細胞凋亡路徑的加乘性分析......................28 第六節 先以薑黃素處理細胞會促使PpIX累積.................................................29 第七節 ALA-PDT與薑黃素作用會增加Autophagy的進行............................30 第四章 討論(Discussion).............................................................................................31 圖與表...........................................................................................................................35 第五章 參考文獻.........................................................................................................53 | |
| dc.language.iso | zh-TW | |
| dc.subject | 薑黃素 | zh_TW |
| dc.subject | 細胞自噬 | zh_TW |
| dc.subject | 細胞凋亡 | zh_TW |
| dc.subject | PpIX | zh_TW |
| dc.subject | 口腔癌 | zh_TW |
| dc.subject | 光動力治療 | zh_TW |
| dc.subject | apoptosis | en |
| dc.subject | PpIX | en |
| dc.subject | Curcumin | en |
| dc.subject | photodynamic therapy | en |
| dc.subject | oral cancer | en |
| dc.subject | autophagy | en |
| dc.title | 薑黃素對於5-氨基酮戊酸光動力治療法應用於口腔癌治療加乘性效應之研究 | zh_TW |
| dc.title | The Study of Synergic Effects of Curcumin on 5-aminolevulinic Acid-Photodynamic Therapy Applied in Oral Cancer | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 江俊斌(Chun-Pin Chiang),郭彥彬(Mark Yen-Ping Kuo) | |
| dc.subject.keyword | 口腔癌,光動力治療,薑黃素,PpIX,細胞凋亡,細胞自噬, | zh_TW |
| dc.subject.keyword | oral cancer,photodynamic therapy,Curcumin,PpIX,apoptosis,autophagy, | en |
| dc.relation.page | 61 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-08-03 | |
| dc.contributor.author-college | 牙醫專業學院 | 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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