Penta-O-Galloyl-β-D-Glucose抑制人類前列腺癌細胞PC-3轉移之分子生物學及生化學研究

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Title:	Penta-O-Galloyl-β-D-Glucose抑制人類前列腺癌細胞PC-3轉移之分子生物學及生化學研究 Molecular and Biochemical Studies on the Suppression of Invasion in Human Prostate Cancer Pc-3 Cells by Penta-O-Galloyl-Β-D-Glucose
Authors:	魏宗德
Contributors:	中國醫藥大學生物科技學系
Keywords:	Prostate;5GG;EGF;MMP-9;Metastasis
Date:	2006-07
Issue Date:	2010-07-15 17:00:32 (UTC+8)
Abstract:	前列腺癌是最常被檢測出來的惡性腫瘤，在西方國家，它在男性死亡率中排名第二。 Matrix metalloproteinases (MMPs)過度表現已經被證實跟癌細胞轉移有很大的關連性，降低這些蛋白質的表現量在臨床上有很大的效用。好幾種最新的MMP 抑制劑已經被研發出來，其中一些已經達到臨床抗癌細胞轉移及治療的效果。在此計劃，我們研究一種從植物中純化出來的植多酚Penta-O-galloyl-β-D-glucose (5GG)對人類前列腺癌細胞PC-3 轉移及抑制MMP-9 表現的影響。我們初步實驗結果顯示5GG 抑制EGF 所引起的細胞轉移及MMP-9 的表現。處理5GG 發現能降低MMP-9 基因轉錄的表現。未來我們將要研究5GG 調控MMP-9 基因表現的機制，例如轉錄因子AP-1 及mitogen-activated protein kinase (MAPK)扮演的腳色都將被探討。此研究計畫的中心理論主要是探討5GG 是否有抑制不需要男性荷爾蒙的前列腺癌細胞PC-3 轉移的潛力。長期的目標是試著利用前列腺癌細胞株PC-3 找出5GG 抑制EGF 誘發MMP-9 表現可能的機制。 Prostate carcinoma is the most frequently diagnosed malignancy and the second leading cause of death in men in western world. Overexpression of matrix metalloproteinases (MMPs) has been known to correlate closely with tumor cell invasion and strategies to down-regulate their expression may ultimately be of clinical utility. METHODS. In this study, in vitro invasion assay was performed by incubating various concentrations of 5GG with 2*104 PC-3 cells for 48 h. We investigated the effects of Penta-O-galloyl-beta-D-glucose (5GG), on the cell invasiveness and MMP-9 induction in human androgen-independent prostate cancer PC-3 cells. The anti-invasive and cytotoxic effects of 5GG were evaluated on human prostate cancer PC-3 cell lines by MTT assays and western blot analyses. RESULTS. 5GG inhibited the EGF-induced cell invasiveness and MMP-9 expression in a dose-dependent manner. 5GG treatment was found to reduce the MMP-9 transcriptional activity. To further study the mechanisms for the 5GG-mediated regulation of MMP-9, the effects of 5GG on transcription factor AP-1 and mitogen-activated protein kinase (MAPK) activities were examined. The results showed that 5GG suppressed the EGF-induced NF-kappaB nuclear translocation and also abrogated the EGF-induced activation of c-jun N-terminal kinase (JNK), which an upstream modulators of NF-kappaB. Finally, we showed that 5GG reduced EGFR expression through proteasome pathway. CONCLUSIONS. These results suggest that 5GG may exert at least part of its anti-invasive effect in androgen-independent prostate cancer by controlling MMP expression through the suppression of EGFR/JNK pathway.
Appears in Collections:	[Department of Biological Science and Technology] Research reports

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