Hispidin對人類肺癌細胞株A549之抗轉移機制探討

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Title:	Hispidin對人類肺癌細胞株A549之抗轉移機制探討 The mechanism of anti-metastasis by Hispidin on human lung carcinoma A549 cell lines
Authors:	陳翔雯;Hsiang-Wen Chen
Contributors:	藥學院中國藥學研究所碩士班
Keywords:	轉移;基質金屬蛋白酶 metastasis;MMP
Date:	2010
Issue Date:	2010-09-29 14:09:43 (UTC+8)
Abstract:	近年來國人的十大死因以惡性腫瘤為首，而肺癌於近幾年漸漸成為惡性腫瘤中主要的死亡原因。癌細胞的轉移往往是造成癌症患者致命的原因之一。癌細胞轉移是一個相當複雜的過程，最重要的是會透過基質金屬蛋白酶(Matrix Metalloproteinases, MMP)的分解作用達到轉移的目的。MMP-2和MMP-9是可分解細胞外基質(extracellular matrix , ECM) 和基底膜 (basement membranes) 的酵素，因此在癌細胞轉移過程中扮演十分重要的角色。Hispidin為桑黃(Phellinus linteus)的主要成分之一，文獻指出桑黃具有抗菌、抗氧化、抗發炎及抗癌等作用，但目前Hispidin 對於肺癌細胞轉移是否有抑制作用，尚無相關文獻探討，因此本實驗就以Hispidin來探討對於人類肺癌細胞株A549之轉移的抑制作用及其機制。由細胞附著(Cell adhesion)、細胞移行(Cell migration) 及細胞傷口癒合 (Cell wound healing) 試驗可看到Hispidin對於A549的爬行及入侵能力有抑制效果。由明膠蛋白酵素電泳法顯示Hispidn可減少MMP-2的活性。利用西方點墨分析可發現Hispidin可增加MMP-2的內生性抑制劑TIMP-2的蛋白質表現，也抑制MMP-2的表現，同時PAI-1的表現增加，亦能間接讓MMP-2的分泌量減少，因此推論Hispidin抑制A549轉移可經由抑制MMP-2表現及增加TIMP-2和PAI-1的蛋白表現量來達到抑制癌細胞轉移的能力。 Metastasis is one of major causes of cancer mortality. Metastasis of cancer cells involves multiple processes and various cytophysiological changes, including changing adhesion capability between cells and extracellular matrix (ECM) and damaging intercellular interaction. Degradation of the ECM and components of the basement membrane is caused by proteinases, such as matrix metalloproteinases (MMPs). Among the MMPs family, MMP-2 and MMP-9 play a critical role in tumor invasion and metastasis, therefore, the inhibition of cell migration or invasion mediated by MMP-2 and MMP-9 could be a preventive way of cancer metastasis. Hispidin is a major component of Phellinus Linteus, one of the traditional Chinese medical herbs. However, the mechanism of Hispidin on anti-metastasis is still unclear. In this study, Hispidin was used to evaluate growth inhibition. The inhibitory effects of Hispidin on growth of tumor cells were determined by MTT assay. Hispidin showed an inhibitory effect on cell migration and invasion by transwell chamber assay. We also found that Hispidin can reduce MMP-2 activity by zymography and Western-blot. Hispidin also induced the endogenous inhibitor, tissue inhibitors of metalloproteinases (TIMPs). These results indicated that Hispidin has a potential anti-metastasis effect on human lung carcinoma cell line A549.
Appears in Collections:	[Graduate Institute of Chinese Medical Science] Theses & dissertations

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