Glabridin抑制人類乳癌細胞的移行、入侵及血管新生之作用機制

CNU IR > Pharmacy and Science > Dept. of Biotechnology (including master's program) > Dissertations and Theses > Item 310902800/23091

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Title:	Glabridin抑制人類乳癌細胞的移行、入侵及血管新生之作用機制 Glabridin inhibits migration, invasion and angiogenesis in human breast cancer
Authors:	吳鈴鈺
Contributors:	莊一全郭柏麟嘉南藥理科技大學：生物科技系暨研究所
Keywords:	Glabridin 轉移侵襲乳癌血管新生 Glabridin breast cancer angiogenesis invasion migration
Date:	2010
Issue Date:	2010-10-12 15:10:56 (UTC+8)
Abstract:	本篇論文發現從甘草分離出的Glabridin可降低人類乳腺癌細胞株MDA-MB-231的移行及入侵，進而達到有效抑制細胞轉移的效果。除此，本研究也證實Glabridin亦可有效抑制MDA-MB-231細胞所造成的血管新生抑制作用。　　Glabridin並無法抑制MDA-MB-231細胞分泌VEGF，因此不屬於間接型抑制血管新生。相對的，Glabridin是藉由直接阻斷人類臍帶靜脈內皮細胞（HUVEC）的移行進而抑制MDA-MB-231細胞所造成的血管新生。在分子機制方面，本研究發現Glabridin可透過增加整合蛋白酶體（integrin）ανβ3降解，進而達到阻斷MDA-MB-231和HUVEC細胞的移行及入侵。Glabridin可進一步減少活化狀態的FAK及Src，並使Src處於Tyr527磷酸化之不活化狀態，而降低其傳遞訊息的能力。Glabridin同時亦能降低FAK與Src的交互作用。再者，Glabridin可降低Akt和ERK1/2的活化，並進一步減少RhoA的活化以致降低肌球蛋白輕鏈（myosin light chain）的磷酸化而抑制細胞移行。最後，以in vivo模式的研究發現，Glabridin能抑制腫瘤血管新生。　　綜合以上的結果證實Glabridin具有高度潛能開發為抗乳癌藥物之天然物，其可透過三種不同方式治療乳腺癌：抑制移行，入侵和血管生成。 This study first report the antimigration, antiinvasive and antiangiogenic effect of glabridin, a flavonoid obtained from licorice, in MDA-MB-231 human breast adenocarcinoma cells. Glabridin exhibited effective inhibition of cell metastasis by decreasing cancer cell migration and invasion of MDA-MB-231 cells. In addition, glabridin also blocked human umbilical vein endothelial cells （HUVEC）migration and decreased MDA-MB-231-mediated angiogenesis. Further investigation revealed that glabridin’s inhibition of cancer angiogenesis was also evident in a nude mice model. Blockade of MDA-MB-231 cells and HUVEC migration was associated with an increase of ανβ3 integrin proteosome degradation. Glabridin also decreased the active forms of FAK and Src, and enhanced levels of inactivated phosphorylated Src（Tyr 527）,decreasing the interaction of FAK and Src. Inhibition of the FAK/Src complex by glabridin also blocked AKT and ERK1/2 activation, resulting in reduced activation of RhoA as well as myosin light chain phosphorylation. This study demonstrates that glabridin may be a novel anticancer agent for the treatment of breast cancer in three different ways: inhibition of migration, invasion and angiogenesis.
Relation:	校內一年後公開，校外永不公開，學年度：98，102頁
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Dissertations and Theses

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