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作 者:张晓玲[1] 王涛[1] 彭纲[1] 张利玲[1] 李跃华[2] 李品东[1] 任精华[1]
机构地区:[1]华中科技大学同济医学院附属协和医院肿瘤中心,湖北武汉430022 [2]南华大学附属第一医院肿瘤内科,湖南衡阳421001
出 处:《中国癌症杂志》2013年第3期188-194,共7页China Oncology
基 金:武汉市科技攻关计划项目(No:201260523172-2)
摘 要:背景与目的:蛋白酶活化受体1(protease-activated receptor 1,PAR1)在肿瘤的侵袭转移中发挥重要作用,其在鼻咽癌中的作用机制尚不清楚。本文旨在检测PAR1活化或抑制对鼻咽癌细胞(CNE1-LMP1)增殖及侵袭的影响,并初探其机制。方法:选取高表达PAR1的CNE1-LMP1细胞系作为研究对象,首先采用四甲基偶氮唑盐(MTT)、划痕实验和Transwell侵袭实验分别检测PAR1特异性激动肽SFLLRN和特异性抑制剂SCH79797对CNE1-LMP1细胞增殖、迁移和侵袭的影响。然后应用实时定量PCR(real-time PCR)和蛋白质印迹法(Westernblot)检测PAR1活化及抑制前后缝隙连接蛋白43(connexin43,Cx43)mRNA及蛋白表达情况,并比较组间表达差异。结果:与CNE1-LMP1细胞未处理组相比,PAR1特异性激动肽SFLLRN能够促进CNE1-LMP1细胞增殖、迁移和体外侵袭,同时发现Cx43 mRNA和蛋白量明显减少(P<0.05)。与CNE1-LMP1细胞未处理组相比,PAR1抑制剂SCH79797能明显抑制CNE1-LMP1细胞增殖、迁移和体外侵袭,并且发现Cx43 mRNA和蛋白量明显增高(P<0.05)。结论:活化PAR1能够促进鼻咽癌细胞系CNE1-LMP1的增殖、迁移和侵袭,减少Cx43 mRNA和蛋白表达,而抑制PAR1的表达能抑制鼻咽癌细胞系CNE1-LMP1的增殖、迁移和侵袭,增加Cx43 mRNA和蛋白表达。Background and purpose: Protease-activated receptor 1 (PAR1) is a key player in the migration and invasion of tumor, but its role in the migration and invasion of nasopharyngeal carcinoma remains unclear. The purpose of this study was to investigate PAR1 on the proliferation and invasion of nasopharyngeal carcinoma cells (CNE1-LMP1) and its mechanism. Methods: Cultured human nasopharyngeal carcinoma cells CNE1-LMP1 were treated with PAR1 synthetic activating peptide SFLLRN or PAR1 antagonist SCH79797, MTT assay, wound-healing and Transwell invasion assay were used to investigate the proliferation, migration and invasion of CNE1-LMP1 ceils. Then the expression of connexin 43 (Cx43) was detected using Western blot and RT-PCR. Results: PAR1 synthetic activating peptide SFLLRN promoted CNE1-LMP1 cell proliferation, migration and invasion, and significantly reduced Cx43 mRNA and protein expression (P〈0.05) compared with the control group. PAR1 antagonist SCH79797 significantly inhibited CNE1-LMP1 cell proliferation, migration, and in vitro invasion ability, and significantly increased Cx43 mRNA and protein expression (P〈0.05) compared with control group. Conclusion: The activation ofPAR1 promotes CNE1-LMP1 proliferation, migration and invasion, and decreases the expression of Cx43 mRNA and protein; the inhibition of PAR 1 inhibits CNE 1-LMP 1 proliferation, migration and invasion, and increases the expression of Cx43 mRNA and protein.
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