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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 郭靜穎 | zh_TW |
| dc.contributor.advisor | Ching-Ying Kuo | en |
| dc.contributor.author | 賈子怡 | zh_TW |
| dc.contributor.author | Tzu-Yi Chia | en |
| dc.date.accessioned | 2024-08-16T17:45:39Z | - |
| dc.date.available | 2024-08-17 | - |
| dc.date.copyright | 2024-08-16 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-08-08 | - |
| dc.identifier.citation | Organization, W.H. Breast cancer. (2024).
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94725 | - |
| dc.description.abstract | 乳癌是全球最常見的癌症之一，也是導致女性死亡的主要疾病。脂質代謝失調為乳癌的重要特徵，許多研究表明脂肪素與乳癌發生風險、進程及預後有密切關係。脂聯素是脂肪素的一種，能夠經由調節脂質和葡萄糖代謝來改善細胞的胰島素敏感性。根據臨床研究，血清中脂聯素降低與高乳癌風險顯著相關，因此後續有多項研究顯示施予脂聯素對癌細胞具有細胞毒性作用。然而，脂聯素的不穩定性和短半衰期是其應用於臨床的潛在阻礙。因此，小分子脂聯素受體促效劑AdipoRon則被提出作為脂聯素替代品。AdipoRon可經由激活脂聯素受體1和2（AdipoR1/2）展示出與脂聯素相似的藥理特性，也能透過阻斷細胞週期或是促進細胞凋亡來抑制癌細胞生長，也因此被視為一種有潛力的抗癌藥物。
在實驗室先前的研究中，已觀察到AdipoRon會增加乳癌細胞中的脂質活性氧類和鐵離子水平，最終導致鐵依賴性死亡。此外， AdipoRon也能在細胞中引起自噬作用且降低運鐵蛋白的快速循環速率。這些初步結果暗示AdipoRon可能經由鐵蛋白自噬引起鐵依賴性死亡。因此本篇研究旨在闡明AdipoRon調節乳癌細胞的鐵相關代謝機制，及其引起的細胞毒性效應。 目前的研究結果顯示AdipoRon會引起鐵蛋白自噬，但不會影響鐵蛋白水平，也不會影響與鐵代謝相關的基因，如TFRC和FTH1。我們也排除細胞中增加的鐵質水平是導致活性氧類水平上升的可能性。另一方面，我們觀察到，AdipoRon可以經由粒線體自噬促進鐵依賴性死亡。此外，AdipoRon可以引起脂肪代謝重組、減少脂肪酸去飽和酶表現量，和減少脂肪油滴的形成。最後，本研究更提出剝奪葡萄糖將使乳癌細胞對AdipoRon感受性更佳，能做為AdipoRon降低治療所需劑量的潛在策略。 | zh_TW |
| dc.description.abstract | Breast cancer is one of the most common cancers worldwide, and also a major disease that leads to female death. Dysregulation of lipid metabolism has been considered as a hallmark of breast cancer. Studies have shown that adipokines are tightly associated with breast cancer risk, progression, and prognosis. Adiponectin, an adipokine, improves the insulin sensitivity of cells by regulating lipid and glucose metabolism. In addition, clinical research shows that lower serum adiponectin levels are significantly associated with a higher risk of breast cancer. Therefore, several studies demonstrate that the administration of adiponectin shows cytotoxic effects against cancer cells. However, poor stability and short half-life are the major limitations of adiponectin in clinical application. Therefore, a small molecule compound, AdipoRon, has been proposed to be a substitute. AdipoRon resembles adiponectin by demonstrating similar pharmacological properties via activating adiponectin receptor 1 and 2 (AdipoR1/2). The molecule has been reported as a potential anti-cancer drug as it also shows cytotoxicity in cancer via apoptosis and cell cycle arrest.
In our previous findings, it was observed that AdipoRon increased lipid ROS and iron levels in breast cancer cells, ultimately resulting in ferroptosis. Additionally, the findings demonstrated an elevated induction of autophagy and reduction in transferrin fast recycling rate in cells treated with AdipoRon. These findings suggest that AdipoRon might induce ferroptosis via ferritinophagy. In this study, we aimed to illuminate the underlying mechanism of AdipoRon regulating iron metabolism in breast cancer cells, and the subsequent cytotoxic effect. Our current findings showed that AdipoRon induces ferritinophagy but does not impact iron-related genes such as TFRC and FTH1. We also ruled out the possibility that elevated iron levels are responsible for the increased ROS pool. On the other hand, we observed that AdipoRon can promote ferroptosis via mitophagy. Additionally, AdipoRon induced lipid metabolic reprogramming, reduced the expression of fatty acid desaturase, and decreased lipid droplet content. Finally, this study suggests that glucose deprivation can enhance the sensitivity of breast cancer cells to AdipoRon, which could serve as a potential strategy to reduce the required therapeutic dose of AdipoRon. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-08-16T17:45:39Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-08-16T17:45:39Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 致謝 i
中文摘要 ii Abstract iii List of Abbreviations v List of Figure x Chapter 1 Introduction 1 Chapter 2 Specific Aim 20 Chapter 3 Materials and Methods 21 Chapter 4 Results 28 Chapter 5 Discussion 35 Figures 39 Appendix 54 Reference 64 | - |
| dc.language.iso | en | - |
| dc.subject | 脂聯素 | zh_TW |
| dc.subject | 乳癌 | zh_TW |
| dc.subject | 鐵依賴性細胞死亡 | zh_TW |
| dc.subject | AdipoRon | zh_TW |
| dc.subject | AdipoRon | en |
| dc.subject | ferroptosis | en |
| dc.subject | adiponectin | en |
| dc.subject | breast cancer | en |
| dc.title | 探討脂聯素受體促效劑AdipoRon 引起乳癌細胞株鐵依賴性死亡之機制 | zh_TW |
| dc.title | Investigating the mechanism of adiponectin receptor agonist, AdipoRon-induced ferroptosis in breast cancer cell lines | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 林亮音;楊雅倩;蘇剛毅;卓爾婕 | zh_TW |
| dc.contributor.oralexamcommittee | Liang-In Lin;Ya-Chien Yang;Kang-Yi Su;Er-Chieh Cho | en |
| dc.subject.keyword | 乳癌,脂聯素,AdipoRon,鐵依賴性細胞死亡, | zh_TW |
| dc.subject.keyword | breast cancer,adiponectin,AdipoRon,ferroptosis, | en |
| dc.relation.page | 72 | - |
| dc.identifier.doi | 10.6342/NTU202403894 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2024-08-08 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學系 | - |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
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| ntu-112-2.pdf 授權僅限NTU校內IP使用（校園外請利用VPN校外連線服務） | 3.38 MB | Adobe PDF |
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