漆黃素抑制人類多形性神經膠質母細胞瘤細胞侵襲之分子機制

中山醫學大學機構典藏 CSMUIR > 醫學院 > 生化微生物免疫研究所 > 博碩士論文 > Item 310902500/10000

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Title:	漆黃素抑制人類多形性神經膠質母細胞瘤細胞侵襲之分子機制 Molecular mechanisms of fisetin inhibit invasion on human glioblastoma multiforme cells
Authors:	林欣慧 Lin, Shin-Huey
Contributors:	中山醫學大學:生化暨生物科技研究所;謝逸憲
Keywords:	漆黃素;人類多形性神經膠質母細胞瘤 Fisetin;Human glioblastoma multiforme cells(GBM)
Date:	2014
Issue Date:	2014-12-10T03:46:23Z (UTC)
Abstract:	原發性腦癌如星狀細胞瘤(Astrocytomas)，可以直接發展成惡性的多形性神經膠質母細胞瘤(Glioblastoma Multiforme；GBM)，或者經過長時間的演變形成GBM，因此能在腦癌細胞演變成惡性腦瘤之前，提早治療和預防，使癌細胞不會侵犯腦組織，將可提高病人存活率。許多研究都在研發新的天然藥物來當作癌症治療藥物或癌症的預防，成為目前重要的課題。漆黃素(Fisetin)屬於類黃酮化合物的一種，目前廣泛用於各種癌症的研究，其具有抗氧化、抗發炎、細胞凋亡、抑制癌細胞增生和侵襲能力，但目前漆黃素對於人類腦癌細胞的作用機制，至今仍然未知。本篇研究以細胞存活率分析(MTT assay)證實低濃度漆黃素不會影響人類腦癌細胞株(GBM8401、U87-MG、Hs683)的細胞存活率。癌細胞的侵襲和轉移是惡性腫瘤的重要特徵之一，因此本研究採用細胞移動和侵襲實驗(Migration and invasion assay)證實漆黃素抑制三株腦癌細胞的移動和侵襲能力。利用人類蛋白質水解酵素晶片 (Human protease array)證實ADAM9、Cathepsin B和Neprilysin蛋白?的表現有明顯下降，此外，使用西方墨點法和RT-PCR驗證漆黃素會抑制ADAM9和Cathepsin B的蛋白和mRNA表現。另外，我們證實漆黃素會專一性誘導ERK磷酸化；同時加入ERK1/2抑制劑(U0126)和轉染siRNA-ERK都會明顯減緩漆黃素抑制ADAM9蛋白和mRNA表現，同時也會減緩漆黃素抑制細胞移動和侵襲作用。此研究結果說明漆黃素未來可能在作為抗腦癌侵襲藥物的發展上深具潛?。 Primary brain cancer such as Astrocytomas that can develop to Glioblastoma Multiforme (GBM) or after a long time to form the GBM.Malignant brain tumors are difficult to be completely removed with surgery, and brain cancer cells resistant to chemotherapy and radiation, even after the treatment is also very easy recurrence, most patients within a year after treatment and death that high mortality rate. Therefore, development of nature drug or drug therapy was important topic. Fisetin belongs to a class of flavonoids, research for a variety of cancers that anti-oxidant, anti-inflammation, anti-tumor, apoptosis and anti-invasion. However, fisetin affect molecular mechanism of human brain cancer is presently unknown. In this study, MTT assay suggested that low concentrations of fisetin not affect cell viability of human brain cancer cell lines (GBM8401、U87-MG、Hs683). Brain cancer cells high invade surrounding normal tissue, led to the invasion of normal tissues necrosis by tumor overgrowth. We found that the fisetin inhibited the migrate and invasive on three brain cancer cells were observed by migration and invasion assay. Using the human proteases array to find that fisetin treatment GBM8401 cells were decreased the ADAM9, Cathepsin B and Neprilysin expression in a dose dependent manner. In addition, fisetin inhibited the protein and mRNA expressions of ADAM9 and Cathepsin B. Moreover, treatment of GBM8401 cells with fisetin induced a sustained activation of the phosphorylation of ERK1/2, and inhibition of ERK1/2 by U0126 or transfection with the siRNA-ERK significantly abolished the fisetin-inhibited migration and invasion through ADAM9 pathway. Therefore, fisetin is a promising candidate for further development as anti-invasive agent against malignant brain cancer progression.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/10000
Appears in Collections:	[生化微生物免疫研究所] 博碩士論文

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