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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 蘇慧敏 | |
dc.contributor.author | Li-Syuan Huang | en |
dc.contributor.author | 黃莉軒 | zh_TW |
dc.date.accessioned | 2021-06-16T08:26:59Z | - |
dc.date.available | 2024-12-31 | |
dc.date.copyright | 2014-02-25 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2014-01-17 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58712 | - |
dc.description.abstract | 脂肪酸合成酶(Fatty acid synthase,FASN)是參與脂肪酸新生(de novo fatty acid synthesis)的重要酵素,目的將糖解作用的產物乙烯輔酶A合成細胞膜中磷脂質的脂肪酸來源,以促進細胞的增生,因此在乳癌細胞中具有高量的表現。在過去研究中已發現,二十二碳六烯酸(Docosahexaenoic acid,DHA)具有抑制乳癌細胞增生的能力,但詳細機制尚被建立。本實驗假設DHA可透過抑制脂肪酸合成酶及其調控路徑來抑制MCF-7的增生作用。人類乳癌細胞MCF-7培養在DHA中 48小時後,分別加入雌二醇及胰島素刺激1小時及24小時,結果發現,在單純加入DHA後,可使AKT及S6磷酸化下降、Sterol regulatory element binding protein precursor form(SREBP1(P))、mature form(SREBP1(M))及FASN蛋白質表現下降,並且使MCF-7增生現象下降,而在給予E2及insulin刺激後,AKT及S6磷酸化上升,SREBP1(P)、SREBP1(M)及FASN蛋白質表現增加,並且使MCF-7增生現象上升,而給予DHA則可抑制其作用;在E2及insulin的刺激下給予PI3K inhibitorLY294002後,發現AKT及S6的磷酸化下降、SREBP1(P)、SREBP1(M)及FASN的蛋白表現下降,而同時加入LY294002及DHA後,DHA可以加強LY294002抑制AKT的磷酸化、SREBP1(P)、SREBP1(M)及FASN的蛋白表現;在E2及insulin的刺激下給予mTOR inhibitor Rapamycin後,發現S6的磷酸化下降,AKT的磷酸化上升、SREBP1(P)及SREBP1(M)的蛋白質表現不受影響,FASN的蛋白質表現則上升,而同時加入DHA及Rapamycin後,DHA可加強Rapamycin抑制S6的磷酸化作用,並且AKT的磷酸化、SREBP1及FASN的蛋白質表現下降。綜合以上結果,DHA能夠抑制AKT和S6的磷酸化、SREBP1(P)、SREBP1(M)及FASN的蛋白質表現量,並且能使MCF-7細胞增生下降,而在E2及insulin的刺激下,DHA亦能抑制其效果。 | zh_TW |
dc.description.abstract | Fatty acid synthase (FASN), the major enzyme for de novo fatty acid synthesis, is highly expressed in the cancer cells. Docosahexaenoic acid (DHA, 22:6n-3) is found to inhibit proliferation of breast cancer cells, but the mechanism is not clear. We then examined the effects of DHA on regulation of FASN expression and proliferation in human breast cancer MCF-7cells. Cells were pretreated with 60 uM DHA, arachidonic acid (AA, 20:4n-6) and oleic acid (OA, 18:1n-9) for 48hrs, and then were stimulated without or with estradiol (E2) or insulin. Supplementation of DHA but not AA and OA decreased the expression of SREBP1 precursor and mature form and FASN. E2 and insulin stimulation increased but DHA decreased the expression of pAKT/AKT, pS6/S6, SREBP1and FASN, and cell proliferation. In addition, DHA enhanced the inhibiting of LY294002 on pAKT signaling for the SREBP1and FASN expression. However, by adding rapamycin, an inhibitor of m-TOR signaling pS6/S6, the FASN expression was increased. We concluded that DHA inhibit pAKT signaling for the expression of SREBP1 and FASN and cell proliferation in MCF-7. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T08:26:59Z (GMT). No. of bitstreams: 1 ntu-102-R00441017-1.pdf: 1830008 bytes, checksum: c04833acb9dc61a97bbe4bad70e19f7d (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 摘要 I
目錄 III 圖表目錄 VI 第一章緒論 (Introduction) 1 一、 乳癌簡介 1 二、癌細胞代謝 2 1.癌細胞之脂肪酸新生(de novo fatty acid biosynthesis in cancer) 2 2.脂肪酸合成酶 (Fatty acid synthase,FASN) 3 3.一般組織的脂肪酸合成酶表現 4 4.癌細胞脂肪酸合成酶的表現 4 三、脂肪酸合成酶(FASN)的調控 5 1.Sterol Regulatory Element Binding Proteins (SREBP) 5 2.Mammalian target of rapamycin (mTOR) 6 四、不飽和脂肪酸(Unsaturated Fatty Acid , UFA) 8 五、n-3多元不飽和脂肪酸對乳癌的效用 9 1.n-3多元不飽和脂肪酸對脂肪酸合成酶的調控 9 2.n-3不飽和脂肪酸對mTOR的影響 10 第二章研究目的 11 一、 研究動機 11 二、 研究假設 11 三、 實驗設計 12 四、 研究之重要性 14 第三章材料與方法 (Materials and Methods) 15 一、 細胞培養 15 二、 細胞之解凍 15 三、 細胞繼代培養 15 四、 不飽和脂肪酸配置 16 五、 Dextran-Charcoal FBS(CD-FBS)製備 17 六、 蛋白質定性與定量分析 18 1. 細胞蛋白質萃取(Whole cell lystates) 18 2. 蛋白質定量 19 3. 電泳檢定-西方墨點法 (Western Blot) 19 4. 轉印(Transfer) 21 5. 酵素免疫染色法 22 七、 Thymidine incorporation assay 24 八、 MTT assay 25 九、 統計方法 25 第四章實驗結果(Result) 26 一、 DHA、OA、AA對MCF-7在有無E2刺激下SREBP1(P)、SREBP1(M)及FASN蛋白質表現的影響 26 二、 DHA、OA、AA對MCF-7在有無insulin刺激下SREBP1(P)、SREBP1(M)及FASN蛋白質表現的影響 26 三、 DHA對MCF-7在給予E2刺激下AKT及其下游mTOR pathway之S6磷酸化影響 27 四、 DHA對MCF-7在給予E2刺激下SREBP1(P)、SREBP1(M)及FASN蛋白質表現的影響 27 五、 DHA對MCF-7在給予insulin刺激下AKT和S6磷酸化的影響 28 六、 DHA對MCF-7在給予insulin刺激下SREBP1(P)、SREBP1(M)及FASN蛋白質表現的影響 28 七、 在E2刺激的環境下,DHA與LY294002(PI3K/AKT inhibitor)對MCF-7中AKT及其下游mTOR pathway之S6磷酸化影響 29 八、 在E2刺激的環境下,DHA與LY294002對MCF-7中SREBP1(P)、SREBP1(M)與FASN蛋白質表現的影響 30 九、 在E2刺激的環境下,DHA與Rapamycin對MCF-7中AKT及其下游mTOR pathway之S6磷酸化的影響 30 十、 在E2刺激的環境下,DHA與Rapamycin對MCF-7中SREBP1(P)、SREBP1(M)與FASN蛋白質表現的影響 31 十一、 在insulin刺激的環境下,DHA與LY294002對MCF-7中AKT與其下游mTOR pathway之S6磷酸化的影響 31 十二、 在insulin刺激的環境下,DHA與LY294002對MCF-7中SREBP1(P)、SREBP1(M)與FASN的影響 32 十三、 在insulin刺激的環境下,DHA與Rapamycin對MCF-7中AKT及其下游mTOR pathway之S6磷酸化的影響 33 十四、 在insulin刺激的環境下,DHA與Rapamycin對MCF-7中SREBP1(P)、SREBP1(M)與FASN蛋白質表現的影響 33 十五、 DHA對MCF-7在給予E2刺激下細胞proliferation及viability的影響 34 十六、 DHA對MCF-7在給予insulin刺激下細胞proliferation的影響: 34 第五章討論(Disscusion) 36 一、 實驗條件之建立 36 1. 細胞株之選擇 36 二、 實驗結果討論 37 1. OA、AA及DHA對MCF-7在有無E2及insulin刺激下SREBP1(P)、 SREBP1(M)及FASN的影響 37 2. DHA對MCF-7在有無E2及insulin刺激下AKT及其下游mTOR pathway之S6磷酸化的影響 38 3. DHA對MCF-7在有無E2及insulin刺激下SREBP1(P)、SREBP1(M)及FASN的影響 40 4. 在E2和insulin的刺激環境下,DHA及LY294002 (PI3K/AKT inhibitor)對於AKT及其下游mTOR pathway 之S6磷酸化、SREBP1(P)、SREBP1(M)及FASN蛋白表現之影響 41 5. 在E2和insulin的刺激環境下,DHA及Rapamycin (mTOR inhibitor)對於AKT及其下游mTOR pathway 之S6磷酸化、SREBP1(P)、SREBP1(M)及FASN蛋白表現影響 42 6. DHA對MCF-7在有無E2及insulin刺激下proliferation的影響 45 第六章總結 46 圖 ( Figure) 47 附錄藥品試劑 60 參考文獻(references) 62 | |
dc.language.iso | zh-TW | |
dc.title | 探討二十二碳六烯酸對人類乳癌細胞株脂肪酸合成酶調控路徑與增生之影響 | zh_TW |
dc.title | Effects of Docosahexaenoic acid on regulation of Fatty acid synthase and proliferation in human breast cancer cell line | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 黃青真,呂紹俊,李明學,趙蓓敏 | |
dc.subject.keyword | 二十二碳六烯酸,脂肪酸合成?,乳癌, | zh_TW |
dc.subject.keyword | Docosahexaenoic acid,fatty acid synthase,breast cancer, | en |
dc.relation.page | 68 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-01-20 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生理學研究所 | zh_TW |
顯示於系所單位: | 生理學科所 |
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