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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 丁詩同(Shih-Torng Ding) | |
| dc.contributor.author | Chi-Chang Huang | en |
| dc.contributor.author | 黃啟彰 | zh_TW |
| dc.date.accessioned | 2021-06-17T05:01:24Z | - |
| dc.date.available | 2028-12-31 | |
| dc.date.copyright | 2018-08-01 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-07-24 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/71258 | - |
| dc.description.abstract | 白色脂肪細胞中，有部分細胞經特定刺激後，會增進粒線體表現去偶合蛋白（Uncoupling protein 1, UCP1）之能力，藉由UCP1蛋白破壞粒線體質子濃度梯度，使粒線體產熱並增加能量消耗，被稱為米色脂肪細胞；透過刺激而表現產熱特性的過程，被稱為褐化（browning），此等細胞與棕色脂肪細胞相似，擁有高數目之粒線體，產熱增加消耗能量之特性，被應用於抵抗肥胖相關代謝症狀，減少脂肪在體內累積所帶來之負面影響。
癌症惡質症（cancer-associated cachexia, CAC）指癌症病患之脂肪及肌肉等體組成不斷流失、體重下降之症狀，失去骨骼肌直接影響病患存活及生活品質，且流失體組成使癌症治療無法承受或產生抗性，有20%癌症病患因癌症惡質症導致死亡。在肺癌、胰臟癌、乳癌之小鼠模型及病患脂肪，發現UCP1之表現提升，暗示癌症具有調控脂肪產熱作用之能力，透過褐化之過程，加劇病患之能量耗損。 為確認癌症是否具有直接影響脂肪產熱基因之表現，收集胰臟癌（Panc-1、BxPC-3、HPAC、MIA-PaCa-2、Capan-1及Capan-2）、乳癌（MDA-MB-231及4T-1）細胞株之條件培養液（conditioned medium），並與細胞株3T3-L1或初代培養之小鼠皮下脂肪細胞（C57BL/6）培養，透過即時聚合酶鏈鎖反應分析生熱(Ucp1, Cidea, Dio2, Prdm16, Cox7a, and Cox8b)及脂肪分解(Atgl and Hsl)之基因表現、再以西方墨點法測量UCP1之蛋白質表現，以及油紅O染色、甘油分析脂肪細胞之油滴堆積。結果顯示，胰臟癌細胞株Capan-1條件培養液在3T3-L1、乳癌細胞株MDA-MB-231及4T-1之條件培養液在小鼠脂肪初代培養，能提高部分產熱基因表現，其UCP1之蛋白質表現經HPAC、Capan-1及MDA-MB-231條件培養液處理後較控制組表現量高，油紅O染色及甘油含量分析結果顯示各處理組與控制組並無顯著差異。 不同之細胞株引起脂肪細胞產熱基因表現之能力不同，而各細胞株中，胰臟癌細胞株HPAC、Capan-1，乳癌細胞株MDA-MB-231及4T-1具有提高部分產熱基因表現之能力，後續的試驗如能證明哪些癌細胞產生的因子會影響脂肪細胞褐化，可應用於減少癌症後期的惡質症對健康的威脅。 | zh_TW |
| dc.description.abstract | Beige adipocytes are a subset of white adipocytes which can dissipate heat under certain stimuli through mitochondrial uncoupling protein 1 (UCP1). Similar to brown adipocytes, high mitochondrial content and energy-consuming characteristic of brown/beige adipocytes have been regarded as a therapeutic target against obesity-related metabolic diseases.
Cancer-associated cachexia (CAC) is a wasting syndrome frequently found in advanced cancer patients with emaciation, muscle weakness and metabolic disorders. Switch of energy-depositing ‘‘bad fat’’ into energy-wasting ‘‘good fat’’ might address a lethal accomplice to cachectic patients. UCP1 expression can be detected in adipose tissues of several cancer models including lung, breast, and pancreatic cancers, suggesting that tumor cells exacerbate cancer progression by operating at adipose thermogenesis. To verify whether the cancer cells can stimulate adipose thermogenesis-related gene expression, conditioned media from pancreatic (Panc-1, BxPC-3, HPAC, MIA-PaCa-2, Capan-1, and Capan-2) and breast (MDA-MB-231 and 4T-1) cancer cell lines were harvested and used to treat mouse cell line 3T3-L1 and primary subcutaneous adipocytes (C57BL/6). The real-time qPCR was conducted to evaluate the thermogenic (Ucp1, Cidea, Dio2, Prdm16, Cox7a, and Cox8b) and lipolysis-related (Atgl and Hsl) gene expression. UCP1 protein level was also determined by Western blotting. Oil-Red O and glycerol release assay were performed for lipid droplet contents and lipolysis. Our results showed that conditioned medium of pancreatic cell line Capan-1 for 3T3-L1, and conditioned medium from breast MDA-MB-231 and 4T-1 for primary adipocyte culture, moderately up-regulated thermogenic gene expression. UCP1 protein expression was higher in adipocytes treated with conditioned-medium of HPAC, Capan-1, or MDA-MB-231 compared to the control group. Analysis of Oil-Red O and glycerol release showed no difference by the different cancer cell derived conditioned media. Taken together, cancer cells might possess differential effects on thermogenic gene expression in adipocytes. Among cell lines used in the study, pancreatic HPAC and Capan-1, breast cancer MDA-MB-231 and 4T-1 partially up-regulated thermogenic gene expression in adipocytes, suggesting the existence of factors in cancer conditioned medium involved in thermogenesis initiation in adipocytes. The identification of the factors that mediates the browning effect can be application in developing strategies for coping with cancer cachexia. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T05:01:24Z (GMT). No. of bitstreams: 1 ntu-107-R04626013-1.pdf: 7425179 bytes, checksum: 126174f03641b377499bf425872bd8d5 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 中文摘要 I
英文摘要 II 目 錄 IV 圖目錄 V 表目錄 VI Introduction 1 Experimental design 15 Materials and methods 16 Results 23 Discussion 39 Reference 47 | |
| dc.language.iso | zh-TW | |
| dc.title | 影響脂肪褐化及脂解之癌症細胞株篩選 | zh_TW |
| dc.title | Screening of potential cancer cell lines on white adipose browning and lipolysis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 沈湯龍(Tang-Long Shen) | |
| dc.contributor.oralexamcommittee | 陳洵一(Shuen-Ei Chen),游玉祥(Yu-Hsiang Yu),林原佑(Yuan-Yu Lin) | |
| dc.subject.keyword | 癌症惡質症,去偶合蛋白,產熱作用,脂肪褐化, | zh_TW |
| dc.subject.keyword | cancer cachexia,thermogenesis,uncoupling protein 1,white adipose browning, | en |
| dc.relation.page | 58 | |
| dc.identifier.doi | 10.6342/NTU201801905 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-07-25 | |
| dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
| dc.contributor.author-dept | 動物科學技術學研究所 | zh_TW |
| 顯示於系所單位： | 動物科學技術學系 | |
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