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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 蔣丙煌(Been-Huang Chiang) | |
dc.contributor.author | Wan-Chi Tsai | en |
dc.contributor.author | 蔡婉琦 | zh_TW |
dc.date.accessioned | 2021-06-16T17:16:57Z | - |
dc.date.available | 2022-02-05 | |
dc.date.copyright | 2012-08-20 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-08-17 | |
dc.identifier.citation | 行政院衛生署衛生統計資訊網
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63709 | - |
dc.description.abstract | 大腸直腸癌(colorectal cancer)在全球癌症致死原因中位居第二,其發生原因與飲食、生活習慣、遺傳等因素相關。腸道的癌化機制是一系列基因突變累積的結果,包含adenomatous polyposis coli (APC)突變使β-catenin表現增加,導致細胞異常增生,產生腺瘤;K-ras的異常表現,使不正常的細胞持續生長,腺瘤加大;p53的突變使異常細胞不會凋亡,最後形成惡性腫瘤。
過去研究顯示,植物內所含的植化素(phytochemicals)具有抑制癌症發生的效果。本研究參考相關文獻,選出六種具有抑制大腸直腸癌潛力的植化素,包括epigallocatechin gallate (EGCG)、sulforaphane (SFN)、phenethyl isothiocyanate (PEITC)、6-shogaol (SG)、ursolic acid (UA)與resveratrol (RV),分別對大腸癌細胞株HT-29及HCT 116進行處理,分析這些植化素對APC、β-catenin、p53等蛋白表現的影響,篩選出能顯著影響上述蛋白表現之植化素,繼而進行代謝體學分析,以了解其作用機制。 結果顯示,resveratrol可有效抑制β-catenin增加、促進wild-type p53表現,並使mutant p53降低,效果最佳。接著進行代謝體分析後發現,resveratrol可抑制大腸癌細胞HT-29及HCT 116之taurine產生、降低HT-29之hypoxanthine與5’-methylthioadensine並提高其CMP;在HCT 116中,resveratrol可提升purine metabolism、TCA cycle及胺基酸相關代謝產物。由此推測,resveratrol可經由對wild-type p53與mutant p53之調控來影響purine metabolism及促進葡萄糖進入TCA cycle產生能量,減少其醣解作用發生,進而達到抑制癌細胞生長之效果。 | zh_TW |
dc.description.abstract | Colorectal cancer (CRC) is the third major cause of cancer-related mortality in Taiwan. The risk factors of CRC include age, family history, inflammatory bowel diseases, and environmental and dietary procarcinogens. In genetic phase, it goes through a series of gene mutations, including APC, β-catenin and p53, from small benign precursor lesions to metastatic carcinomas. Based on information from literatures, this study chose six phytochemicals, including epigallocatechin gallate (EGCG), sulforaphane (SFN), phenethyl isothiocyanate (PEITC), 6-shogaol (SG), ursolic acid (UA) and resveratrol (RV), to investigate their effect on HT-29 and HCT 116 colorectal cancer cells in terms of regulating APC, β-catenin and p53. Then we selected the most effective one for further metabolic profile analysis. Results showed that resveratrol can suppress β-catenin, mutant p53 expression and increase wild-type p53 expression. And the metabolic profiling indicated that resveratrol can reduce taurine in both colorectal cancer cells, decrease hypoxanthine and 5’-methylthioadensine, enhance CMP in HT-29 cells. In HCT 116 cells, resveratrol is able to raise purine metabolism, TCA cycle and amino acid related metabolites. In conclusion, resveratrol may affect purine metabolism and TCA cycle by regulating wild-type p53 and mutant p53 expression. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T17:16:57Z (GMT). No. of bitstreams: 1 ntu-101-R99641027-1.pdf: 6565790 bytes, checksum: 3cc88f2247603b9097f37bce20f8ce87 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 口試委員審定書 I
謝誌 II 摘要 III Abstract IV 目錄 V 圖目錄 VIII 表目錄 X 第一章、 前言 1 第二章、 文獻整理 2 第一節、 大腸直腸癌 2 2.1.1 大腸直腸癌的種類與分期 4 2.1.2 大腸直腸癌的危險因子 7 2.1.3 大腸直腸癌之基因致癌機轉 10 第二節、 植化素 phytochemicals 20 2.2.1 植化素的種類與生理活性 20 2.2.2 植化素的生理活性與大腸直腸癌之關係 24 第三節、 代謝體 metabolomics 28 2.3.1 分離偵測方法與統計分析 28 2.3.2 應用 28 第三章、 研究目的與實驗架構 29 第一節、 研究目的 29 第二節、 實驗架構 29 第四章、 實驗材料與方法 31 第一節、 實驗材料與儀器設備 31 4.1.1 細胞株來源 31 4.1.2 藥品試劑 31 4.1.3 儀器設備 33 第二節、 實驗方法 34 4.2.1 樣品配製 34 4.2.2 細胞培養 34 4.2.3 細胞存活率分析 35 4.2.4 蛋白質萃取與定量(Bradford, 1976) 37 4.2.5 SDS-PAGE電泳分析(Shapiro et al., 1967) 38 4.2.6 西方墨點法(Western blotting)(Towbin et al., 1979) 40 4.2.7 細胞週期分析(Flow cytometry analysis) 41 4.2.8 代謝體分析(由臺灣大學基因體學研究中心協助分析) 43 4.2.9 統計分析 44 第五章、 結果 45 第一節、 植化素SFN、PEITC、SG、UA、RV與EGCG對人類大腸直腸癌細胞株HT-29存活率之影響 45 第二節、 植化素SFN、PEITC、SG、UA與RV對人類大腸直腸癌細胞株HCT 116存活率之影響 47 第三節、 利用西方墨點法探討SFN、PEITC、SG、UA、RV對大腸癌細胞中APC、β-catenin、mutant p53、wild-type p53蛋白表現之影響 49 第五節、 RV對大腸癌細胞株HT-29與HCT 116細胞週期之影響 61 第六節、 RV對大腸癌細胞株HT-29與HCT 116代謝產物之影響 63 第六章、 討論 69 第七章、 結論 82 第八章、 參考文獻 84 附錄 期刊格式 99 | |
dc.language.iso | zh-TW | |
dc.title | 植化素對大腸直腸癌之抑制機制與營養代謝體之分析 | zh_TW |
dc.title | The inhibition mechanism and metabolic profile of phytochemicals in colorectal cancer cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 何其儻(Chi-Tang Ho),鍾景光(Jing-Gung Chung),吳明賢(Ming-Shiang Wu) | |
dc.subject.keyword | 大腸直腸癌,植化素,營養代謝體學,p53,resveratrol, | zh_TW |
dc.subject.keyword | colorectal cancer, phytochemicals,metabolomics,p53,resveratrol, | en |
dc.relation.page | 108 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-08-18 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 食品科技研究所 | zh_TW |
顯示於系所單位: | 食品科技研究所 |
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