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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 潘敏雄(Min-Hsiung Pan) | |
dc.contributor.author | Chen Lin | en |
dc.contributor.author | 林辰 | zh_TW |
dc.date.accessioned | 2021-06-16T02:31:24Z | - |
dc.date.available | 2017-08-03 | |
dc.date.copyright | 2015-08-03 | |
dc.date.issued | 2015 | |
dc.date.submitted | 2015-07-30 | |
dc.identifier.citation | Aggarwal, B. B.; Takada, Y.; Oommen, O. V., From chemoprevention to chemotherapy: common targets and common goals. Expert opinion on investigational drugs 2004, 13, 1327-38.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/53852 | - |
dc.description.abstract | Calebin-A 是從薑黃中分離出的類薑黃素化合物。先前研究指出其具有抑制人類胃腺癌細胞生長及誘導人類肝癌細胞凋亡的功效,然而在腸癌細胞中的抗癌活性機制尚不明確,因此本篇目的為探討calebin-A之抗腸癌功效與其相關分子機制,此外,本實驗更進一步使用異種移植動物模式探討calebin-A對腫瘤生長之影響。結果顯示,calebin-A具有抑制人類腸癌細胞HCT116生長之活性,流式細胞儀分析指出calebin-A誘導細胞停滯於S和G2/M期,在分子機制上,流式細胞儀與彗星電泳結果指出,經calebin-A處理使胞內活性氧分子 (Reactive oxygen species, ROS) 含量增加與引起DNA損傷,隨後上調r-H2AX、磷酸化chk1、chk2、p53與p53、p21之蛋白質表現量、降低cdc25A、 cyclinB、 cyclinA與cdc2表現量,經自由基清除劑N-乙醯基半胱氨酸 (N-acetyl-L-cysteine, NAC) 預處理後,能回復細胞週期的分布,表示ROS可能參與calebin-A所誘導的細胞週期停滯之途徑。在異種移植模式中,評估calebin-A對於HCT116體內異種移植之抗腫瘤活性,以腹腔注射方式給予裸calebin-A (25 mg/kg) 能顯著降低腫瘤體積,組織染色分析指出,calebin-A能減小腫瘤細胞及降低細胞增生指標 (Proliferating cell nuclear antigen, PCNA) 蛋白質表現量。綜合上述實驗結果,calebin-A在體外及體內模式中皆呈現抗人類腸癌細胞之潛力,據此可作為腸癌化學預防劑開發之重要依據。 | zh_TW |
dc.description.abstract | Calebin-A is a curcuminoids compound isolated from turmeric. Previous studies indicated that calebin-A inhibits cell growth and induces apoptosis in drug-resistant human gastric cancer cells and also restrain the proliferation of human hepatoma cell line HepG2 cells; however, the molecular mechanism of anti-cancer activity in colon cancer remains unclear. Therefore, the objectives of research are to study the anti-cancer efficacy of calebin-A and its underlying molecular mechanism. Furthermore, we use xenograft animal model to further investigate the anti-tumor effect of calebin-A. The results showed calebin-A was able to inhibit colon cancer cells growth and induced cell cycle to arrest in S and G2/M phase. At the molecular levels, calebin-A exhibited the anti-cancer ability by increasing reactive oxygen species (ROS) level and triggering DNA damage response as evidenced by flow cytometry and comet assay. Western blot analysis showed calebin-A up-regulation of phosphorylation of H2AX, chk1, chk2, p53 and p53, p21 protein levels, decreased cdc25A, cyclinB, cyclinA and cdc2 protein levels. Moreover, pretreatment of N-acetyl-L-cysteine (NAC) reversed the cell cycle population, indicated ROS might involve in the cell cycle arrest signaling pathway caused by the toxic of calebin-A. In the xenograft model, we evaluated the anti-tumor ability of calebin-A on HCT116 tumor xenografts in vivo. Intraperitoneal injection of calebin-A (25 mg/kg) to nude mice significantly decreased tumor volume as well as reduced tumor size and proliferating cell nuclear antigen (PCNA) protein by Hematoxylin & Eosin (HE) and immunohistochemistry (IHC) stain, respectively. These results suggested calebin-A with potent anti-cancer effect in vitro and in vivo, could provided a molecular basis for the development of colon cancer chemopreventive agent. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T02:31:24Z (GMT). No. of bitstreams: 1 ntu-104-R02641019-1.pdf: 4185089 bytes, checksum: b585ecc057affefb40f973af677e70d6 (MD5) Previous issue date: 2015 | en |
dc.description.tableofcontents | 目錄
誌謝 i 中文摘要 iii Abstract iv 目錄 v 附圖目錄 ix 圖目錄 xi 縮寫表 xii 第壹章、文獻整理 1 第一節 大腸癌 ( Colorectal cancer, CRC )之介紹 1 (一) 統計資料 1 (二) 大腸的構造及功能 1 (三) 大腸癌 ( Colorectal cancer ) 3 (四) 影響大腸癌形成過程之基因表現 3 (五) 大腸癌的分期 5 (六) 導致形成人類大腸癌之危險因子 6 (七) 預防及治療人類大腸癌之方法 7 第二節 細胞週期 (Cell cycle) 12 (一) 介紹 12 (二)細胞週期的調控 13 (三)細胞週期檢查點(Cell cycle checkpoints) 15 (四)細胞週期停滯之機制 16 (五)細胞週期停滯和癌症的發展 18 第三節 細胞死亡的方式 18 (一) 細胞自噬(Autophagy) 18 (二) 細胞凋亡(Apoptosis) 20 (三) 細胞壞死 (Necrosis) 24 (四) 細胞自噬、細胞凋亡與細胞壞死之間的交互作用 27 第四節 活性氧分子 (Reactive oxygen species, ROS) 28 (一) 活性氧分子與氧化壓力(oxidative stress) 28 (二) ROS對癌症的影響 29 第五節 薑黃及其萃取物(Curcuminoids)介紹 30 (一)薑黃介紹及其功效 30 (二) 類薑黃素化合物 (Curcuminoids) 31 (三) Calebin-A 31 第貳章、實驗目的及架構 33 第一節 實驗目的 33 第二節 實驗架構 34 (一) 體外試驗(in vitro) 34 (二) 體內試驗 (in vivo) 35 第參章、實驗材料及方法 36 第一節 實驗材料 36 (一)藥品試劑 36 (二)儀器設備 39 第二節 實驗方法 41 (一)樣品製備 41 (二) 細胞培養 41 (三) 細胞存活率分析或細胞增殖分析 (MTT test) 41 (四)細胞自噬之分析 42 (五) Annexin V/PI雙染之分析 43 (六) 細胞週期分布分析 43 (七) 蛋白質電泳 (SDS-PAGE) 與西方墨點法 44 (八)彗星電泳試驗 (Comet assay) 48 (九) 胞內ROS產生量分析 49 (十) 抗氧化劑NAC對於細胞毒性之影響 50 (十一) 抗氧化劑NAC對於細胞週期之影響 51 (十二) 動物實驗 51 (十三) 動物腫瘤組織包埋與切片 52 (十四) 蘇木精-伊紅染色法 (Hematoxylin and eosin stain) 53 (十五) 免疫組織染色法 (Immunohistochemistry, IHC) 54 (十六) 統計分析 56 第肆章、實驗結果與討論 57 第一節 Calebin-A 對於人類腸癌株HCT116生長之影響 57 第二節 高濃度Calebin-A 誘導HCT116細胞壞死及細胞自噬 57 第三節Calebin-A 誘導HCT116細胞週期停滯和凋亡 58 第四節 Calebin-A誘導細胞週期停滯之分子機制 59 第五節Calebin-A 誘導DNA損傷並啟動細胞週期檢查點 60 第六節Calebin-A 增加胞內ROS的含量 61 第七節ROS參與calebin-A誘導細胞週期停滯之途徑 62 第八節Calebin-A對於異種移植之影響 62 第九節Calebin-A對於腫瘤組織切片之影響 63 第伍章、結論 66 第陸章、圖表 67 | |
dc.language.iso | zh-TW | |
dc.title | Calebin-A誘導人類腸癌細胞週期停滯並抑制腫瘤細胞生長之體外及體內試驗研究 | zh_TW |
dc.title | Calebin-A induces human colon cancer cell cycle arrest and inhibits tumor cell growth in vitro and in vivo | en |
dc.type | Thesis | |
dc.date.schoolyear | 103-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 游若?(Roch-Chui Yu) | |
dc.contributor.oralexamcommittee | 李銘仁(Ming-Ren Li),何元順(Yuan-Soon Ho),何其儻(Chi-Tang Ho) | |
dc.subject.keyword | Calebin-A,細胞週期,大腸癌,類薑黃素化合物,異種移植, | zh_TW |
dc.subject.keyword | Calebin-A,cell cycle,colon cancer,curcuminoids,xenograft, | en |
dc.relation.page | 95 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2015-07-30 | |
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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