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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 潘敏雄 | |
dc.contributor.author | Nien-Chi Chen | en |
dc.contributor.author | 陳念琦 | zh_TW |
dc.date.accessioned | 2021-06-17T06:12:58Z | - |
dc.date.available | 2019-02-14 | |
dc.date.copyright | 2019-02-14 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-10-05 | |
dc.identifier.citation | 衛生福利部國民健康署。104 年健康報表。
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/71873 | - |
dc.description.abstract | 結腸直腸癌 (colorectal cancer) 是目前備受重視的健康議題,其發病原因與飲食習慣、肥胖及發炎性大腸疾病相關,而肥胖可能透過提高促發炎因子如 tumor necrosis factor-α (TNF-α)、interleukin-6 (IL-6) 及調節脂肪酸攝取與運送的脂肪酸結合蛋白 fatty acid-binding protein 5 (FABP5) 之表現而促進結腸直腸癌的發展。紫檀芪 (pterostilbene, PTS) (3,5-dimethoxy-4’hydroxystilbene) 隸屬於多酚類化合物 stilbenoids,存在於蔓越莓及藍莓中,是 resveratrol 的相似物,已知具有抗氧化、降低膽固醇、抗肥胖及抗腫瘤的活性,因此本研究將進一步評估在 adipocyte conditioned-medium (aCM) 誘導人類腸癌細胞 HT29 惡性轉型過程中,PTS 的預防功效以及調節分子機制。結果證實,PTS 可以抑制aCM 所刺激的轉錄因子 nuclear factor-kappa B (NF-kB)、b-catenin 及 peroxisome proliferator-activated receptor g(PPAR-g) 的活性,而這些轉錄因子經由其上游的 phosphoinositide 3-kinase (PI3K)、protein kinase B (Akt)、p38 mitogen-activated protein kinase (p38 MAPK)、extracellular signal-regulated kinase (ERK) 及 c-Jun N-terminal kinases 1/2 (JNK1/2) 等訊息傳遞路徑所活化,這些路徑可以藉由給予 PTS 後被抑制,繼而減少腸癌細胞中 FABP5 的基因及蛋白質表達,同時也降低了促轉移因子 vascular endothelial growth factor (VEGF)、matrix metalloproteinase-2 (MMP2) 和 MMP9 的蛋白質表現,並且能進一步抑制 MMP2 和 MMP9 的酵素活性,更減少分泌到胞外的 TNF-a。本實驗亦發現,利用經 TNF-a 抗體中和後的 aCM 培養 HT29 之後,能使原本被誘發的 FABP5、VEGF、MMP2 與 MMP9 之表現具有減少的現象。綜合以上結果建議,PTS 可以從基因層面調控 FABP5 的訊號途徑,抑制肥胖微環境所誘導的人類腸癌細胞之遷移,進而達到減緩肥胖相關之腸癌惡質化。 | zh_TW |
dc.description.abstract | Colorectal cancer (CRC) is a worldwide health issue related to diet habit, obesity and inflammatory bowel disease (IBD). Obesity could promote CRC development by increasing the secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and the expression of fatty acid-binding protein (FABP5). Pterostilbene (PTS) (3,5-dimethoxy-4’hydroxystilbene), a natural dimethylated analog of resveratrol, is a phenolic compound with diverse pharmacologic activities including anti-inflammatory, antioxidant, anti-obesity and antitumor. However, its potential for inhibiting obesity-related CRC remains unclear. Our study evaluated the mechanism of inhibitory effects of PTS on adipocyte conditioned-medium (aCM)-induced malignant transformation in HT29 colorectal adenocarcinoma cells. Results showed that PTS could downregulate the expression of aCM-induced FABP5 and pro-metastasis factors such as vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP2), MMP9 and extracellular tumor necrosis factor alpha (TNF-a via inhibiting aCM-induced nuclear factor-kappa B (NF-kB), b-catenin and peroxisome proliferator-activated receptor g(PPAR-g). Moreover, PTS can suppress aCM-stimulated phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinases 1/2 (JNK 1/2) signaling pathways activation which are upstream of NF-kB, b-catenin and PPAR-g. Based on our findings, we suggested that PTS could aliviate adiposity-induced cachexia in CRC via inihibiting cell migration through downregulating FABP5 gene expression. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T06:12:58Z (GMT). No. of bitstreams: 1 ntu-107-R05641007-1.pdf: 4669133 bytes, checksum: 9cfd94b451a5b06219e5e03ee4cb623c (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 口試委員會審定書 #
謝誌 I 中文摘要 III Abstract V 目錄 VII 附圖目錄 X 附表目錄 XI 圖目錄 XII 表目錄 XIII 縮寫表 XIV 第一章、 文獻回顧 1 第一節、 肥胖與結腸直腸癌 1 1.1.1. 結腸直腸癌之簡介 1 1.1.2. 肥胖之簡介及定義 3 1.1.3. 肥胖與結腸直腸癌之關係及相關分子機制 5 1.1.4. 脂肪細胞與腸癌細胞之互惠關係 8 1.1.5. 脂肪酸於癌細胞中扮演的角色 9 第二節、FABP5之分子訊息傳遞路徑 12 1.2.1. FABPs之簡介 12 1.2.2. FABP5之簡介 14 1.2.3. FABP5與肥胖之關係 14 1.2.4. FABP5與癌症之關係 15 1.2.5. FABP5於肥胖相關癌症中之訊息調控路徑 17 第三節、紫檀芪 (Pterostilbene) 19 1.3.1. 簡介 19 1.3.2. 紫檀芪已知功效 20 第二章、 實驗目的與架構 22 第一節、 研究目的 22 第二節、 實驗架構 22 第三章、 材料與方法 24 第一節、 實驗材料 24 3.1.1. 儀器設備 24 3.1.2. 試劑藥品 25 第二節、 樣品來源及製備 26 3.3.1. 細胞培養 27 3.3.2. 製備adipocyte conditioned-medium (aCM) 28 3.3.3. 油紅染色 (Oil red O stain) 29 3.3.4. 細胞增生率試驗 (MTT assay) 30 3.3.5. 細胞存活率試驗 (Trypan blue assay) 31 3.3.6. 蛋白質萃取 32 3.3.7. 蛋白質定量 32 3.3.8. 西方墨點法 (Western blotting) 33 3.3.9. 明膠蛋白酵素電泳法 (Gelatin zymography) 37 3.3.10. 傷口癒合試驗 (Wound healing assay) 39 3.3.11. 逆轉錄聚合酶鏈式反應 (Reverse transcription-PCR, RT-PCR) 39 3.3.12. 即時聚合酶鏈式反應 40 3.3.13. 洋菜凝膠電泳分析 (Agarose gel electrophoresis, AGE) 41 3.3.14. TNF alpha 與 IL-6 Mouse ELISA Kit 43 第四節、 統計分析 46 第四章、 結果與討論 47 第一節、 腸癌細胞株之 FABP5 表現量 47 第二節、 以 aCM 刺激人類腸癌細胞 (HT29) 分泌 MMP2 及 MMP9 酵素與蛋白質誘發腫瘤細胞 migration 的作用,同時誘發 FABP5 之表現,評估 pterostilbene 之抑制功效,並探討其調控的分子機制與訊息傳遞路徑 48 4.2.1. Pterostilbene (PTS) 及 aCM 對 HT29 細胞存活率之影響 48 4.2.2. PTS 對於 aCM 誘發 HT29 細胞遷移 (migration) 之影響 49 4.2.3. PTS 可以抑制 aCM 誘發基質金屬蛋白酶 (MMP2 及 MMP9) 的酵素活性以及 MMP2, MMP9 與血管內皮生長因子 (VEGF) 的蛋白質表現 49 4.2.4. PTS 可以抑制 aCM 誘發脂肪酸攜帶蛋白 (FABP5) 的基因表達進而減少其蛋白質表現 50 4.2.5. PTS 對於 aCM 誘導轉錄因子 b-catenin、NF-kB 和 PPAR-g 活性之影響 51 4.2.6. PTS 對於 aCM 活化 HT29 細胞內 MAPK 和 PI3K/Akt 訊息傳遞路徑之影響 52 第三節、 aCM 藉由 TNF-a 誘發人類腸癌細胞 (HT29) 惡性轉型 54 4.3.1. 抗 TNF-a 的抗體對 aCM 誘發 HT29 細胞遷移之影響 54 4.3.2. 抗 TNF-a 的抗體對 aCM 誘發 MMP2、MMP9 及 VEGF 表現的影響 55 4.3.3. 抗 TNF-a 的抗體對 aCM 誘發 FABP5 基因及蛋白質表現的影響 55 第五章、 結論 57 第六章、 圖表 58 第七章、 參考文獻 74 | |
dc.language.iso | zh-TW | |
dc.title | 紫檀芪經由 FABP5 訊號路徑抑制肥胖促進腸癌細胞遷移 | zh_TW |
dc.title | Pterostilbene inhibits adipocyte conditioned-medium-induced colorectal cancer cell migration through targeting FABP5 related signaling pathway | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 何元順,黃步敏,郭靜娟,王應然 | |
dc.subject.keyword | 結腸直腸癌(colorectal cancer),肥胖,fatty acid-binding protein 5 (FABP5),紫檀? pterostilbene (PTS),adipocyte conditioned-medium (aCM), | zh_TW |
dc.subject.keyword | colorectal cancer (CRC),obesity,fatty acid-binding protein 5 (FABP5),pterostilbene (PTS),adipocyte conditioned-medium (aCM), | en |
dc.relation.page | 83 | |
dc.identifier.doi | 10.6342/NTU201804181 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2018-10-05 | |
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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