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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳彥榮 | |
| dc.contributor.author | You-Chun Lin | en |
| dc.contributor.author | 林宥君 | zh_TW |
| dc.date.accessioned | 2021-07-11T15:40:26Z | - |
| dc.date.available | 2023-08-24 | |
| dc.date.copyright | 2018-08-24 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-08-13 | |
| dc.identifier.citation | Abate-Shen, C. (2002). Deregulated homeobox gene expression in cancer: cause or consequence? Nat Rev Cancer, 2(10), 777-785.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79058 | - |
| dc.description.abstract | 癌幹細胞具有較強的抗化療藥物以及轉移能力，因此不易治療根除，被認為是導致癌症復發及轉移的原因。Egr-1 為轉錄因子可以調控細胞的增生及凋亡，也會促使幹細胞的分化。而在癌症的研究中發現 Egr-1 同時作為促癌基因和抑癌基因，但是目前還不清楚 Egr-1 對於癌幹細胞的影響。本篇研究在大腸癌細胞株 DLD1 中過量表現及削弱 Egr-1，並藉由球體及群落形成檢測、群落抗藥性試驗、邊緣族群分析、大腸癌幹細胞標記表現量檢測以及轉移能力分析，發現 Egr-1 會透過抑制癌幹細胞的自我更新，降低其族群數量，以及促使分化。此外，我發現給予大腸癌細胞株 DLD1，常山植物的萃取物處理後，會促進 Egr-1 蛋白質的表現，並且也會降低癌幹細胞的族群數量及特性，代表著常山萃取物可能是透過促進 Egr-1 來達成抑制癌幹細胞的功效。未來可以利用這些藥物，使病患腫瘤組織中，癌幹細胞群減少甚至消失，進而降低癌症的復發以及轉移，增加治療的成功率。 | zh_TW |
| dc.description.abstract | Cancer stem cells (CSCs) are the small population cells in tumor and have the ability of self-renewal to maintain themselves and differentiation into various non-stem cancer cells. CSCs are responsible for tumor progression, drug resistance, metastasis and cancer recurrence. Early growth response-1 (Egr-1), a zinc finger transcription factor, is involved in regulation of cell proliferation, apoptosis and stem cell differentiation. In cancer, Egr-1 has a dual role as both an oncogene and a tumor suppressor. Therefore, Egr-1 may play an important role in CSCs. In this study, I demonstrated that Egr-1 could inhibited self-renewal ability of CSCs to form spheres and colonies. The ratio of side population and colorectal CSCs markers were reduced. In addition, Egr-1 could also suppress drug resistance and migration of CSCs. These data demonstrated that Egr-1 could reduce the number of CSCs in cancer through inhibition of self-renewal and inducing CSCs differentiation. Furthermore, after treatment of Dichroa febrifuga extract, Egr-1 protein expression was upregulated in colorectal cancer cells, and the abilities of CSCs, such as self-renewal and drug resistance, were inhibited. These evidences revealed that Dichroa febrifuga extract had an antitumor effect may associate with the induction of Egr-1. Therefore, Dichroa febrifuga extract might be useful for decreasing or even eliminating CSCs in tumor mass. This method might be a CSCs target therapy to prevent tumor recurrence and metastasis. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:40:26Z (GMT). No. of bitstreams: 1 ntu-107-R05b22021-1.pdf: 6077730 bytes, checksum: 1743250e38c3b18cfbb40a50882b1de1 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 中文摘要i
Abstractii 1. 文獻回顧1 1.1 大腸癌與癌幹細胞1 1.1.1 大腸癌1 1.1.2 癌幹細胞1 1.2 Early growth response gene 1 (Egr-1)4 1.2.1 概述4 1.2.2 調控細胞的生長與凋亡5 1.2.3 促進幹細胞的分化5 1.2.4 與癌症的關係6 1.2.5 與癌幹細胞的關係8 1.3 中草藥常山植物萃取物與純物質 Halofuginone (HF) 9 1.3.1 常山萃取物、常山鹼、Halofuginone (HF)9 1.3.2 Halofuginone (HF) 與癌症10 1.3.3 Halofuginone (HF) 與 Egr-112 2. 材料與方法14 2.1 細胞培養14 2.2 質體建構14 2.3 病毒製作15 2.4 病毒力價 (virus titer) 測定15 2.5 病毒轉染 (virus transfection)16 2.6 RNA萃取16 2.7 定量即時聚合酶連鎖反應 (quantitative real-time PCR, qRT-PCR)17 2.8 細胞蛋白質萃取17 2.9 十二烷基硫酸鈉聚丙烯醯胺膠體電泳 (Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, SDS-PAGE) 與西方墨點法 (Western blotting)17 2.10 抗藥性測試 (drug resistance)18 2.11 球體形成試驗 (sphere formation assay)19 2.12 群落形成 (colony formation assay) 及群落抗藥性試驗 (Drug resistance of colony formation assay)19 2.13 Transwell 細胞遷移試驗 (Transwell migration assay)19 2.14 邊緣族群 (side population)20 2.15 常山萃取物樣品製備21 2.16 統計分析21 3. 結果22 3.1 過量表現 Egr-1 會降低癌幹細胞的族群數量並且抑制自我更新22 3.2 削弱 Egr-1 增加癌幹細胞數量並且降低癌幹細胞進行分化22 3.3 常山萃取物促進 Egr-1 的蛋白質表現23 3.4 常山萃取物降低癌幹細胞數量24 3.5 Halofugione (HF) 促進 Egr-1 的蛋白質表現24 3.6 Halofugione 降低癌幹細胞的族群數量 25 4. 討論26 4.1 Egr-1 的影響26 4.1.1 Egr-1 抑制癌幹細胞的自我更新26 4.1.2 Egr-1 減少癌幹細胞的數量27 4.1.3 Egr-1 抑制癌幹細胞的抗藥性27 4.1.4 Egr-1 抑制癌細胞的轉移能力28 4.1.5 Egr-1 影響大腸分化基因的表現28 4.2 常山萃取物與 HF 的影響29 4.2.1 常山萃取物抑制癌細胞的生長29 4.2.2 常山萃取物促進 Egr-1 的表現，來抑制癌幹細胞29 4.2.3常山萃取物的成分組成30 4.2.4 HF促進 Egr-1 的表現，來抑制癌幹細胞31 5. 結果圖33 圖 1: 過量表現 Egr-1 會抑制癌幹細胞維持族群數量36 圖 2: 削弱 Egr-1 增加癌幹細胞的族群數量42 圖 3: 常山萃取物促進 DLD1 表現 Egr-149 圖 4: 常山萃取物降低癌幹細胞的族群數量52 圖 5: Halofuginone (HF) 促進 DLD1 表現 Egr-154 圖 6: Halofuginone 降低癌幹細胞的族群數量56 6. 附錄表56 附錄表 1. qRT-PCR 引子57 附錄表 2. 抗體59 7. 參考文獻60 附錄 – 英文版70 Abstract70 Introduction72 Material and Methods76 Results83 Discussion88 Figures93 Supplementary Tables101 References103 | |
| dc.language.iso | zh-TW | |
| dc.subject | 分化 | zh_TW |
| dc.subject | 大腸癌 | zh_TW |
| dc.subject | 癌幹細胞 | zh_TW |
| dc.subject | Egr-1 | zh_TW |
| dc.subject | 常山萃取物 | zh_TW |
| dc.subject | Egr-1 | en |
| dc.subject | colorectal cancer | en |
| dc.subject | differentiation | en |
| dc.subject | Dichroa febrifuga extract | en |
| dc.subject | cancer stem cell | en |
| dc.title | Egr-1 於大腸癌幹細胞之功能研究 | zh_TW |
| dc.title | The Role of Egr-1 in Colorectal Stem Cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 黃楓婷,蔡素宜 | |
| dc.subject.keyword | 大腸癌,癌幹細胞,Egr-1,常山萃取物,分化, | zh_TW |
| dc.subject.keyword | colorectal cancer,cancer stem cell,Egr-1,Dichroa febrifuga extract,differentiation, | en |
| dc.relation.page | 106 | |
| dc.identifier.doi | 10.6342/NTU201803179 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-08-13 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| dc.date.embargo-lift | 2023-08-24 | - |
| 顯示於系所單位： | 生化科技學系 | |
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