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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 許麗卿(Lih-Ching Hsu) | |
| dc.contributor.author | Ching-Chun Huang | en |
| dc.contributor.author | 黃靖鈞 | zh_TW |
| dc.date.accessioned | 2021-06-08T07:08:46Z | - |
| dc.date.copyright | 2011-10-07 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-12 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/26396 | - |
| dc.description.abstract | 頭頸癌的治療方針是以TNM (T: 腫瘤; N: 淋巴; M: 轉移) 癌症分類來給予治療建議。頭頸癌包括口腔至咽喉部所有的鱗狀上皮癌，近年來在台灣罹患口腔癌的病人逐年增加。儘管有些生物標記已被用來研究化學放射療法的結果預測，目前尚無有效的個人化標記可以預測治療效果，因此，我的研究目的是在探討在口腔癌有過度表現的細胞週期蛋白D1(cyclin D1)或蛋白磷酸酶1a(PP1a)是否可以用來當作癌症化學治療的反應標記。
我們評估四株口腔癌細胞的cyclin D1或PP1a表現和藥物敏感性，利用MTT assay來測定cisplatin抑制50%細胞生長之藥物濃度 (cisplatin的IC50)，結果發現含有高表現量的cyclin D1和PP1a的細胞對於cisplatin有較高的感受性，四株口腔癌細胞cisplatin的IC50範圍從2 uM到15 uM，SCC131對藥物最敏感而SCC104的藥物感受性最差，其中SCC131的cyclin D1和PP1a蛋白質表現量都最高，反之SCC104都是最低的。因此利用siRNA的技術，針對cyclin D1或PP1a進行knockdown來確認cyclin D1或PP1a與cisplatin感受性的影響是否有關係，結果發現利用siRNA將cyclin D1的表現量降低時，細胞對於cisplatin的感受性降低，IC50從1.8 uM提高到4.3 uM；相同的結果也發現到在另一株cyclin D1表現量較高的細胞 (SCC036)，IC50從9.5 uM提高到15.3 uM；除此之外，也看到細胞對於5-FU的感受性也降低了。此外，從cisplatin促進細胞凋亡活性的角度，利用Western analysis偵測caspase 3的活化和利用cell cycle analysis觀察sub-G1的族群，也看到若將cyclin D1進行knockdown會減少細胞凋亡的活性。綜合以上的結果，cyclin D1會增加cisplatin和5-FU對於口腔癌細胞的藥物感受性。 相反地，若將SCC131和SCC103兩株表達較多PP1a的細胞進行knockdown會增加低劑量的cisplatin (1 uM and 3 uM) 和5-FU (2 uM) 的藥物感受性。把cyclin D1或PP1a進行knockdown卻得到兩種截然不同的結果。我們利用pRB蛋白 (retinoblastoma protein) 的作用、細胞週期和藥物的作用機轉來探討其中可能的原因和機制，以共同解釋所發現的現象。最後也進一步利用一個簡單的模型來說明cyclin D1和PP1a對於口腔癌細胞藥物感受性的影響。cyclin D1使細胞進入細胞週期的複製相 (S phase)，而S phase為cisplatin和5-FU最容易攻擊的階段；另一方面，PP1a的作用恰巧與cyclin D1是相反的，會使得細胞無法順利進入細胞週期，導致抗癌藥物無法發揮效用。 從建立的細胞實驗發現，對於cyclin D1表現量較高細胞對於藥物的感受度是較敏感的。雖然我們發現將PP1a進行knockdown會些許增加低劑量的cisplatin和5-FU的藥物感受性，但單純比較cisplatin的敏感性與PP1a的表現量似乎沒有關聯性。因此由得到的結果來支持提出的假說，cyclin D1表現量的高低是可以來做為預測藥物感受性的因子，對於未來的口腔癌治療可以提供個人化療程的參考資訊。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2021-06-08T07:08:46Z (GMT). No. of bitstreams: 1 ntu-100-R98423023-1.pdf: 2004657 bytes, checksum: d44d157621d310d1bcc37f6ab46d1023 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 口試委員會審定書
誌謝 i 中文摘要 ii ABSTRACT iv CONTENTS vi LIST OF FIGURES viii LIST OF TABLES x Chapter 1 Introduction 1 1.1 Head and neck cancer 1 1.1.1 Epidemiology 1 1.1.2 Risk factors 2 1.1.3 Clinical staging of oral cavity cancer 2 1.1.4 Treatments of oral cavity cancer 3 1.2 Chromosone band 11q13 amplification in OSCC cells 3 1.2.1 Cyclin D1 4 1.2.2 PP1a 5 3.1 Chemicals and reagents 23 3.2 OSCC cell lines and cell culture 23 3.3 Cell growth assays 23 3.2.1 MTT assay 23 3.2.2 SRB assay 24 3.2.3 Colony formation assay 24 3.4 Western analysis 25 3.5 siRNA transfection and drug treatment schedule 26 3.6 Cell cycle analysis 27 Chapter 4 Results 29 4.1 Cisplatin sensitivity and 11q13 amplification in OSCC cell lines 29 4.2 Cyclin D1 knockdown by siRNA decreases the expression level of cyclin D1 in SCC131 cells 30 4.3 Cyclin D1 depleted cells are more resistant to cisplatin and 5-FU treatment 30 4.4 Knockdown of cyclin D1 decreases apoptosis induced by cisplatin in SCC131 cells 31 4.5 PP1a depleted cells are more sensitive to low-dose cisplatin and 5-FU treatment 31 4.6 Cyclin D1 and PP1a regulate cisplatin sensitivity in part by modulating pRB phosphorylation 32 Chapter 5 Discussion 46 Chapter 6 Conclusions 50 REFERENCES 52 | |
| dc.language.iso | en | |
| dc.subject | cisplatin | zh_TW |
| dc.subject | 口腔癌 | zh_TW |
| dc.subject | 細胞週期蛋白D1 | zh_TW |
| dc.subject | 蛋白磷酸酶 | zh_TW |
| dc.subject | 1a | zh_TW |
| dc.subject | PP1a | en |
| dc.subject | cisplatin | en |
| dc.subject | OSCC | en |
| dc.subject | cyclin D1 | en |
| dc.title | 探討cyclin D1與PP1a對口腔癌細胞之藥物感受性的影響 | zh_TW |
| dc.title | The effect of cyclin D1 and PP1a on chemosensitivity of oral squamous cell carcinoma cell lines | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 楊家榮(Chia-Ron Yang),陳燕惠(Yen-Hui Chen) | |
| dc.subject.keyword | 口腔癌,細胞週期蛋白D1,蛋白磷酸酶,1a,cisplatin, | zh_TW |
| dc.subject.keyword | OSCC,cyclin D1,PP1a,cisplatin, | en |
| dc.relation.page | 58 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2011-08-12 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| 顯示於系所單位： | 藥學系 | |
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