Dkk3在肝母细胞瘤细胞中的作用及机制研究

项目名称： Dkk3在肝母细胞瘤细胞中的作用及机制研究

项目编号： No.81201893

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 裴一花

作者单位： 厦门大学

项目金额： 23万元

中文摘要： 肝母细胞瘤是小儿最常见的肝脏原发性恶性肿瘤。近年来对患儿进行综合治疗，显著提高了HBL的治疗效果，但其死亡率仍高达20%-30%。因此寻求新的HBL预防、诊断及治疗方法具有重要的意义。Dkk3/REIC目前被认为是一种抑癌基因。有研究发现异常Dkk3表达所致细胞表型异常在恶性肿瘤发生和演进过程中发挥重要作用。前期研究发现Dkk3基因、蛋白在肝母细胞瘤和肝细胞肝癌中均过表达，在肝母细胞瘤其表达更为广泛，并且在肝母细胞瘤细胞系中有表达。本课题拟通过利用人肝母细胞瘤细胞株、离体和动物实验，对基因转染后"高表达"和"沉默"Dkk3的肝母细胞瘤细胞株和荷瘤鼠模型进行对比研究，检测Dkk3基因表达异常对肝母细胞瘤细胞的增殖能力、凋亡情况和侵袭能力等生物学性状的影响以及生物体内的作用：揭示Dkk3在肝母细胞瘤中的作用及机制。为临床以Dkk3作为肝母细胞瘤基因治疗新靶点提供理论依据。

中文关键词： Dkk3；肝母细胞瘤细胞系；凋亡；侵袭；细胞增殖

英文摘要： Hepatoblastoma (HBL) is the most common primary liver malignancy in children. Nevertheless, a clear understanding of the pathogenesis is lacking.Comprehensive treatment of HBL has significantly improved in recent year, but its mortality rate is still in 20%-30%.Therefore,seeking a new method of prevention, diagnosis and treatment of HBL is of great significance.Dickkopf 3 (Dkk-3), also known as Reduced Expression in Immortalized Cells (REIC),has been implicated as a tumor suppressor exhibiting down-regulation in several tumor tissues and cell lines.Aberrant expressin causes cell phenotype abnormal, which can play an important role in the formation and development of the malignant tumor.Our previous study demonstrated that Dkk3 was overexpressed in HBLs and HCCs, and that its expression was more frequent in the former than in the latter. Based on our previous study, we will investigate the role and mechanism of the Dkk3 gene in hepatoblastoma by using human hepatoblastoma cell line, in vitro experiments and tumor-bearing animals experiments through the methods of DKK3 transfection and knock-down. To clarify the function of DKK3 in HBL by using the methods of cell proliferation, apoptosis and cell invasion assay.The goal of this study is to evaluate the clinical and pathological features of hepatoblastomas and to

英文关键词： Dkk3；Hepatobalastoma cells；Apoptosis；Invasion；cell proliferation