請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64168完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 何?芳(Yunn-Fang Ho) | |
| dc.contributor.author | Ya-Ju Lee | en |
| dc.contributor.author | 李亞儒 | zh_TW |
| dc.date.accessioned | 2021-06-16T17:33:06Z | - |
| dc.date.available | 2017-09-19 | |
| dc.date.copyright | 2012-09-19 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-15 | |
| dc.identifier.citation | 參考文獻
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64168 | - |
| dc.description.abstract | 研究背景
肝癌 (hepatocellular carcinoma; HCC) 根據統計為世界上第六名常見癌症及因癌症而死亡原因的第三名。目前對於肝癌的治療有很多種，包括手術切除、移植、全身性化療及雷射灼燒，但由於肝癌在早期不好診斷、治療後復發率高及藥物毒性和抗藥性關係，對於肝癌的治療效果大打折扣；因此，研發出新穎治療肝癌的方法或藥物是必須的。 在許多的傳統中藥材當中有很多的活性成份有研究指出具有抗癌效果，當歸(danggui或dongquai ; Angelica sinensis)是其中一種。當歸最早根據古籍記載主要作用是補血、活血、調經止痛，現在則有促進血液循環、改善免疫系統、治療經期疾病及促進排便效果；而最近文獻指出當歸具有抗癌作用，進一步分析後發現在當歸中的一種活性成份n-butylidenephthalide (n-BP)會藉由影響不同標的，包括細胞週期、端粒酶、血管新生及內質網，造成癌細胞生長抑制並進一步導致細胞凋亡。 研究目的 在本研究中，以人類肝癌細胞Hep3B作為體外研究模式的對象，我們利用n-BP處理癌細胞，研究藥物在Hep3B中對於其細胞生長抑制、細胞凋亡及訊息路徑的影響。 研究方法 本研究以n-butylidenephthalide為主要實驗藥物：我們先利用SRB 生長抑制實驗 (SRB assay)確定藥物IC50後，接著以流式細胞儀分析細胞週期變化及使用西方墨點法觀察在經過n-BP處理後相關蛋白質的變化，以便後續的生長抑制及死亡機制探討。 研究結果 細胞生長抑制實驗中(SRB assay)中，Hep3B在8種不同藥物濃度處理48小時下，發現細胞抑制生長有呈現劑量關係，隨著藥物濃度提高其抑制生長比率也變多，經由三次的結果計算後n-BP在Hep3B中的IC50為368.98 μM，於是採用超過IC50的藥物濃度 (500 μM )進行之後的細胞週期及細胞凋亡機制探討。在細胞週期實驗中發現和控制組相比，經過藥物處理後細胞明顯停在G0/G1並造成明顯Sub-G1 (細胞凋亡)增加。進一步研究n-BP處理後的生長抑制及細胞死亡機制，藥物處理後1小時發現phospho-signal transducer and activator of transcription 3 (p-STAT-3；Tyr705)和控制組相比明顯降低，發現cyclin E, cyclin D1, p-P70S6K表現量有明顯減少。此外，在p-Akt1 (Ser473)及p-janus kinase 2 (p-JAK-2; Tyr1007/1008)表現量和控制組相比，有隨著時間點而跟著變少。 結論 本研究中發現，n-BP處理後會經由抑制JAK2-STAT3這條訊息路徑抑制下游基因 (cyclin D1)轉錄，並同時抑制cyclin E及p-P70S6K表現，導致Hep3B細胞生長抑制，並進一步造成細胞死亡。未來若能針對其詳細造成細胞死亡的機轉、n-BP溶解度問題及n-BP半衰期過短的問題做深入的探討及改善的話，對之後n-BP的開發及應用在臨床治療上有更大的進展。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2021-06-16T17:33:06Z (GMT). No. of bitstreams: 1 ntu-101-R98423014-1.pdf: 2002479 bytes, checksum: 37d9ecbeb101ce3598e77bb3747d943a (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 目錄
中文摘要.............................................................................................I 英文摘要...........................................................................................III 圖目錄............................................................................................VIII 表目錄..............................................................................................IX 英文名詞與簡稱對照表.........................................................................X 第壹章 文獻探討...........................................................................1 1. 當歸綜述.........................................................................................1 1.1 當歸簡介及用途.........................................................................1 1.2 當歸活性成份及藥理作用............................................................2 1.2.1 正丁烯基苯酞 (n-Butylidenephthalide) .......................................2 1.2.2 藁本內酯 (z-Ligustilide) .........................................................4 1.2.3 洋川芎內酯A (Senkyunolide A) ...............................................5 2 癌症..............................................................................................6 2.1 癌症特性...................................................................................6 2.1.1 生長訊號自給自足 (Self-Sufficiency in Growth Signals).................6 2.1.2 抑制性生長訊號不敏感 (Insensitive to Anti-Growth Signals) .........7 2.1.3 細胞凋亡逃離 (Evasion of Apoptosis) ......................................8 2.1.4 無限制複製 (Limitless Replication) ........................................10 2.1.5 持續性血管新生 (Sustained Angiogenesis)................................11 2.1.6 組織侵犯與轉移 (Tissue Invasion and Metastasis).......................12 2.1.6.1 Integrins.......................................................................12 2.1.6.2 Cadherins.....................................................................12 2.1.6.3 基質金屬蛋白酶 (Matrix Metalloproteinases，MMPs).....................13 2.2 訊息傳遞路徑 (Signal Transduction Pathways)..................................................14 2.2.1 RAF/MEK/ERK Signaling Pathway.........................................................14 2.2.2 PI3K/AKT/ mTOR Signaling Pathway.....................................................16 2.2.3 STATs Signaling Pathway.........................................................................18 第貳章 研究動機.........................................................................20 第參章 實驗材料.........................................................................21 1. 實驗藥品......................................................................................................................21 2. 抗體..............................................................................................................................22 3. 實驗儀器......................................................................................................................23 第肆章 實驗方法.........................................................................25 1. 細胞實驗......................................................................................................................25 1.1 細胞培養...............................................................................................................25 1.2 細胞計數...............................................................................................................25 1.3 細胞存活率分析...................................................................................................25 1.4 細胞凋亡分析.......................................................................................................26 1.5 細胞週期同步實驗...............................................................................................27 1.6 西方墨點法...........................................................................................................28 第伍章 實驗結果.........................................................................31 1. n- Butylidenephthalide 之細胞存活率分析................................................................31 2. n- Butylidenephthalide 對細胞週期及細胞凋亡影響................................................32 2.1 不同濃度n-BP之影響.........................................................................................32 2.2 不同時間n-BP處理對細胞週期及細胞凋亡影響.............................................34 2.3 細胞週期同步後n-BP對細胞週期及細胞凋亡影響.........................................37 3. n- Butylidenephthalide 對細胞凋亡及相關蛋白表現之影響....................................39 4. n- Butylidenephthalide對SOCS3及Akt-1磷酸化表現之影響...............................41 5. Thymidine 處理後n- Butylidenephthalide對細胞凋亡及相關蛋白表現之影響....43 6. Thymidine 處理後JAK-2磷酸化對STAT-3磷酸化的影響...................................45 7. Thymidine 處理後Akt-1磷酸化對STAT-3磷酸化的影響.....................................46 第陸章 討論.................................................................................47 第柒章 結論與未來發展方向.....................................................52 參考文獻........................................................................................53 | |
| dc.language.iso | zh-TW | |
| dc.subject | 正丁烯基苯酞 | zh_TW |
| dc.subject | 生長抑制 | zh_TW |
| dc.subject | 肝癌 | zh_TW |
| dc.subject | JAK-2/ STAT-3訊息路徑 | zh_TW |
| dc.subject | 當歸 | zh_TW |
| dc.subject | JAK-2/STAT-3 signaling pathway | en |
| dc.subject | growth inhibition | en |
| dc.subject | danggui | en |
| dc.subject | hepatocellular carcinoma | en |
| dc.subject | n-butylidenephthalide | en |
| dc.title | 當歸萃取物n-Butylidenephthalide對Hep3B之
抗腫瘤作用機轉探討 | zh_TW |
| dc.title | A Mechanism Study on the Anti-neoplastic Actions of n-Butylidenephthalide from Angelica sinensis on Hep3B | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 孔繁璐(Fan-Lu Kung),顧記華(Jih-Hwa Guh) | |
| dc.subject.keyword | 肝癌,當歸,正丁烯基苯酞,JAK-2/ STAT-3訊息路徑,生長抑制, | zh_TW |
| dc.subject.keyword | hepatocellular carcinoma,danggui,n-butylidenephthalide,JAK-2/STAT-3 signaling pathway,growth inhibition, | en |
| dc.relation.page | 68 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-08-15 | |
| 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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