離胺基氧化？對口腔癌血管新生之影響

中國醫藥大學機構典藏 China Medical University Repository, Taiwan > 健康照護學院 > 口腔衛生學系 > 研究計畫 > Item 310903500/11585

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题名:	離胺基氧化？對口腔癌血管新生之影響
其它题名:	The Study of Lysyl Oxidase (LOX) Mediated Angiogenesis in Oral Squamous Cell Carcinoma
作者:	謝宗明(Shieh Tzong-Ming)
贡献者:	健康照護學院口腔衛生學系
日期:	2009-07-31
上传时间:	2009-09-01 15:18:09 (UTC+8)
摘要:	離胺基氧化酶(lysyl oxidase，LOX)是一種需依賴銅離子才具活性的酵素，其功能為氧化lysine幫助膠原蛋白與彈性蛋白鍵結。目前對LOX屬致癌或抑癌基因仍未釐清，先驅研究中以檳榔子萃取物ANE (areca nut extract)刺激人類正常口腔上皮細胞及OSCC細胞株OECM-1後24小時LOX mRNA皆被誘發；而OSCC組織的LOX mRNA與protein亦比正常組織高，由臨床統計知LOX mRNA表現不利於淋巴轉移。將OSCC細胞株SAS之LOX靜默後可促進SAS轉移與侵襲能力，但抑制非貼附性生長與腫瘤生長能力，多項證據顯示LOX 對OSCC影響甚鉅。當LOX過度表現時利於腫瘤生長，但SAS或OECM-1中的LOX靜默或過度表現皆不影響細胞生長曲線，故推測LOX可能與血管新生有關。本研究計畫有三目標：（一）建立LOX穩定過度及靜默之OSCC細胞株，以BrdU鑲嵌、PCNA及P105表現、細胞生長曲線等驗證細胞增生是否受LOX影響。（二）以血管內皮細胞及單核球U937，分別加入LOX過度及靜默細胞之培養液、LOX抑制劑-APN共同培養，在in vitro狀況下觀察內皮細胞血管分化，與U937而分泌血管新生因子情形。(三)將LOX過度表現細胞打入裸鼠觀察腫瘤生長，並將腫瘤切片觀察血管分布，確認LOX與血管新生之關聯，另染CD31標誌判斷是否有管脈發生前驅細胞聚集現象。本研究期藉由分子生物技術了解在口腔癌化組織中LOX促進腫瘤生長之機制，以提昇分子醫學之進展。 Areca nut use is the major cause of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis （OSF） in Eastern and Southern Asians. Areca nut contains a high level of free copper ions. Lysyl oxidase (LOX) is a copper-activated enzyme critical for extracellular matrix organization. Contradictory evidence has been put forward to suggest that LOX may be either an oncogenic or a suppressive element. In previous study, both normal human oral keratinocyte （NHOK） and OECM-1, an oral cancer cell line, LOX mRNA expression were induced by areca nut extract （ANE） treatment after 24 h. Up-regulation of LOX mRNA and LOX protein expression in OSCCs relative to adjacent oral mucosa were found. Knock-down of LOX induced cellular migration and invasion but it reduced the anchorage-independent growth and xenographic tumorigenesis of OSCC cells. LOX exerts oncogenic roles in areca-associated OSCC. In previous study, silence LOX expression of SAS inhibited xenographic tumorigenesis ability, and enhanced when LOX overexpressed. However, the SAS and OECM-1 proliferation rate did not affect by LOX abnormal expression. Beside LOX can affect tumor metastasis, LOX expression also affect primary tumor growth. It is interesting overexpressed LOX how to help primary tumor growth. Angiogenesis is the one of major factors to determine tumor growth. So LOX might have some relations between angiogenesis. There are three aims in the study：（1） set up LOX overexpression and silence OSCC cell line, and confirm whether LOX affect cell growth.（2） whether LOX direct and indirect interaction with angiogenesis in vitro. (3) in vivo model test whether LOX affect vasculogenesis and angiogenesis. The overall achievements of this grant will enhance our understanding on LOX whether a positive factor for OSCC angiogenesis. The findings may be beneficial for the interception of oral carcinogenesis in further preclinical study
显示于类别:	[口腔衛生學系] 研究計畫

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