Taipei Medical University Institutional Repository:Item 987654321/61265
English  |  正體中文  |  简体中文  |  全文笔数/总笔数 : 45422/58598 (78%)
造访人次 : 2540731      在线人数 : 271
RC Version 7.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜寻范围 查询小技巧：
  • 您可在西文检索词汇前后加上"双引号"，以获取较精准的检索结果
  • 若欲以作者姓名搜寻，建议至进阶搜寻限定作者字段，可获得较完整数据
    •  进阶搜寻


    jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://libir.tmu.edu.tw/handle/987654321/61265


    题名: 有機陽離子轉運蛋白 OCT2 增強胰臟癌細胞對 oxaliplatin 藥物敏感性之研究
    Organic cation transporter 2 sensitizes pancreatic cancer cells to oxaliplatin
    作者: 毛晨柔
    MAU, CHEN-ZOU
    贡献者: 代謝與肥胖科學研究所碩士班
    邱慶豐
    关键词: 胰臟癌;有機陽離子運輸蛋白2;多重抗藥性
    pancreatic cancer;organic cation transporter 2;multiple drug resistance
    日期: 2021-06-22
    上传时间: 2022-01-02 22:28:47 (UTC+8)
    摘要: 目前胰臟癌的藥物治療包含gemcitabine、FOLFIRINOX和oxaliplatin等，然而治療效果常因抗藥性受限。有機陽離子運輸蛋白2 (organic cation transporter 2)，主要負責腎臟中含鉑藥物的運輸，如oxaliplatin。先前研究發現於多種癌症組織中，OCT2的表現量較正常組織少；而使用甲基化抑制劑decitabine可增加腎臟細胞癌中OCT2的表現量，進而提高癌細胞對oxaliplatin的敏感性。本研究藉由分析線上資料庫和從北醫聯合人體資料庫取得的檢體組織發現，OCT2基因在的於胰臟癌腫瘤組之表現顯著較正常控制組織組低。另外，胰臟癌抗gemcitabine藥物細胞株會影響OCT2蛋白的表現和功能，且OCT2蛋白表現與胰臟癌細胞株對oxaliplatin的敏感性呈現正相關。進一步研究探討OCT2表現背後的調控機制，發現具gemcitabine抗藥性的胰臟癌細胞株PANC-1/GR細胞中的OCT2啟動子幾個位點相較PANC-1細胞受到較高的甲基化情形。而decitabine可顯著增加PANC-1/GR細胞的OCT2表現和其對oxaliplatin的敏感性。另外，線上資料庫也呈現OCT2和DNA-甲基轉移酶 (DNMT1)呈現顯著的負相關，顯示OCT2的轉錄表現可能受到DNMT1甲基化的調控所抑制。除DNA甲基化的調控外，本研究還探討胰臟癌細胞株中OCT2受到蛋白酶體降解的情形，發現OCT2不論於胰臟癌細胞株或抗藥細胞株皆會受到蛋白酶體的降解作用。因此，結合decitabine或MG132與oxaliplatin都可能為胰臟癌治療帶來新治療策略。
    Gemcitabine, FOLFIRINOX and oxaliplatin have been chemo-therapy drugs for pancreatic cancer, however, the efficiency of these drugs are usually limited due to drug-resistance. Organic cation transporter 2 (OCT2), being a platinum drug transporter, mainly expresses on renal proximal tubule cells. Previous studies have shown that the expression of OCT2 is lower in several cancer tissues compared to its individual health control tissues. Based on Oncomine online database and the tissue samples collected from Joint BioBank of Taipei Medical University, OCT2 level of pancreatic tumor are significantly lower expression compared to its individual health control tissue samples. Moreover, we found that gemcitabine resistance of pancreatic cancer cells (PANC-1/GR and MIA Paca-2/GR) and parental PANC-1 and MIA Paca-2 cells were shown the positive correlation between OCT2 level and oxaliplatin. We further studied the underlying mechanism the regulation of OCT2 expression and found that OCT2 promoter region of PANC-1/GR cells have higher methylation frequency on several CpG sites compared to PANC-1 cells. Decitabine (DNA methyltransferase 1 inhibitor) treatment reversed the protein expression of OCT2 and enhanced the sensitivity of oxaliplatin in PANC-1/GR cells. Additionally, OCT2 and DNMT1 were shown significantly a negative correlation in pancreatic cancer tissues from Oncomine database, suggesting that transcription of OCT2 might be down-regulated by DNMT1 methylation. Besides regulation by DNA methylation, our study further investigated the protein degradation of OCT2 in pancreatic cancer cells. Proteasome inhibitors MG132 treatment was shown that OCT2 might go through proteasome degradation between PANC-1 and PANC-1/GR cells. In conclusion, combination of decitabine or MG132 with oxaliplatin treatments provide potential therapeutic strategies for pancreatic cancer.
    描述: 碩士
    指導教授：邱慶豐
    委員：張綺芬
    委員：吳泓璁
    数据类型: thesis
    显示于类别:[代謝與肥胖科學研究所] 博碩士論文

    文件中的档案:

    档案 描述 大小格式浏览次数
    index.html0KbHTML594检视/开启


    检视Licence

    在TMUIR中所有的数据项都受到原著作权保护.

    TAIR相关文章

    著作權聲明 Copyright Notice

    • 本平台之數位內容為臺北醫學大學所收錄之機構典藏，包含體系內各式學術著作及學術產出。秉持開放取用的精神，提供使用者進行資料檢索、下載與取用，惟仍請適度、合理地於合法範圍內使用本平台之內容，以尊重著作權人之權益。商業上之利用，請先取得著作權人之授權。

      The digital content on this platform is part of the Taipei Medical University Institutional Repository, featuring various academic works and outputs from the institution. It offers free access to academic research and public education for non-commercial use. Please use the content appropriately and within legal boundaries to respect copyright owners' rights. For commercial use, please obtain prior authorization from the copyright owner.

    • 瀏覽或使用本平台，視同使用者已完全接受並瞭解聲明中所有規範、中華民國相關法規、一切國際網路規定及使用慣例，並不得為任何不法目的使用TMUIR。

      By utilising the platform, users are deemed to have fully accepted and understood all the regulations set out in the statement, relevant laws of the Republic of China, all international internet regulations, and usage conventions. Furthermore, users must not use TMUIR for any illegal purposes.

    • 本平台盡力防止侵害著作權人之權益。若發現本平台之數位內容有侵害著作權人權益情事者，煩請權利人通知本平台維護人員([email protected])，將立即採取移除該數位著作等補救措施。

      TMUIR is made to protect the interests of copyright owners. If you believe that any material on the website infringes copyright, please contact our staff([email protected]). We will remove the work from the repository.

    Back to Top
    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回馈