合成吳茱萸次鹼衍生物對上皮-間質轉移之抑制作用

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題名:	合成吳茱萸次鹼衍生物對上皮-間質轉移之抑制作用 The Study of Biochemical Actions of Rutaecarpine Derivatives on Suppressing the Epithelial-Mesenchymal Transition
作者:	王琪 Wang, Chi
關鍵詞:	發炎;移動;侵襲;上皮-間質轉移;吳茱萸次鹼衍生物;migration;invasion;Epithelial-Mesenchymal Transition;Rutaecarpine Derivatives
日期:	2013-07-03
上傳時間:	2018-11-12 14:45:59 (UTC+8)
摘要:	細胞轉移的起始需要侵入而侵入由上皮-間質轉移所達到，上皮間質轉移是指上皮細胞失去細胞極性及細胞間的附著力的過程，並且得到移動與侵襲的特性而轉變成間質細胞。在發炎的情形底下，由巨噬細胞分泌的前發炎細胞激素所造成的微環境導致細胞之移動與侵襲都會是造成癌症發展的原因。吳茱萸次鹼，為中草藥吳茱萸的成分之一，曾展現抗腫瘤與抗發炎的能力，為了找尋更好的防癌藥物，本實驗室使用新合成的吳茱萸次鹼衍生物並篩檢其生物活性，期許能有更好的抗癌症能力，於是聚焦在研究新穎的合成吳茱萸次鹼衍生物之抗發炎及抗上皮間質轉移能力。在本篇中使用脂多醣來刺激Raw264.7巨噬細胞作為研究模型來證實吳茱萸次鹼衍生物的抗發炎能力，數據顯示吳茱萸次鹼衍生物可抑制一氧化氮的生成、iNOS、COX-2、前發炎細胞激素TNFα這些與發炎相關的因子，以及NFκB的活性。此外，在A2780卵巢癌細胞中吳茱萸次鹼衍生物亦抑制了細胞的移動與侵襲能力，且抑制SUMO-1、上皮間質轉移相關之轉錄因子Snail之蛋白表現。顯示吳茱萸次鹼衍生物具有抗發炎及抗上皮間質轉移的效果，因此極有潛力做為新型的抑癌候選藥物。 Deactivated Epithelial–Mesenchymal transition (EMT) is a mechanism to prevent cancer cell to become metastasis. EMT is a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal cells. The microenvironment formed by the pro-inflammatory cytokine macrophage cells secreted under the inflammatory state contributes to cancer development in terms of invasion and metastasis. Rutaecarpine, the constituent of Chinese herb Evodiae fructus, exhibited anti-tumor activities and anti-inflammatory effect. The synthetic rutaecarpine derivatives thus were screened for better effect on cancer prevention . We investigated the newly synthesized rutaecarpine derivatives’s anti-inflammatory effect and and anti-EMT effect. In this study, lipopolysaccharide was used to stimulate Raw264.7 macrophage cells as model to confirm the effect of rutaecarpine derivatives on anti-inflammation. Rutaecarpine derivatives inhibited the release of nitrite oxide (NO), and the protein level of iNOS, COX-2, Nrf2, pro-inflammatory cytokine TNFα which are associated with the inflammation, and NFκB activity. In addition, rutaecarpine derivatives also showed inhibition to A2780 ovarian carcinoma cell’s motility and invasiveness; protein level of SUMO-1, EMT related transcriptional factor Snail were also inhibited in A2780 cell. This suggests that rutaecarpine derivatives have anti-inflammation effect that potentially become novel candidates for cancer suppression.
描述:	碩士委員-黃聲東委員-吳瑞裕指導教授-林俊茂
資料類型:	thesis
顯示於類別:	[醫學科學研究所] 博碩士論文

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