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异常凝血酶原(DCP)促进人血管内皮细胞增殖与迁移作用研究

es-γ-carboxy prothrombin increase the proliferation and migration of human vascular endothelial cells

中文摘要英文摘要

es-γ-carboxyl prothrombin (DCP)是由肝细胞肝癌产生的异常凝血酶原,肝癌病人血液和肝组织高表达DCP可能表示恶性程度高和预后不良。本项研究以体外实验法检查了DCP刺激人血管内皮细胞增殖现象,在肝癌增殖过程中所起的作用,分析了其刺激肝癌微血管增殖的机制。MTT法结果显示,DCP明显地刺激ECV304细胞增殖,并呈现作用时间和剂量依赖性关系。划痕实验显示,DCP能够持续性地刺激内皮细胞迁移速度和距离。以Transwell小室法证实,DCP能够明显地刺激血管内皮细胞突破Matrigel覆盖的人工基底膜,显示可能具有促进细胞浸润与转移的能力。进一步实验,将人血管内皮细胞接种于人工形成3-D的Matrigel中,模拟形成肿瘤微血管环境。结果显示,DCP明显刺激细胞形成微血管。在这些实验观察基础上,进一步以Western blotting和ELISA实验法分析了与肝癌形成和发展最相关的一些蛋白因子表达水平,包括EGFR,VEGF和MMPs。结果显示,DCP能够刺激这些血管形成相关因子的表达水平,显示可能与肝癌的浸润与转移有关。结论:DCP可能在肝癌增值、浸润与转移以及微血管形成过程中起到至关重要的作用。

es-γ-carboxy prothrombin (DCP) is an aberrant prothrombin produced by hepatocellular carcinoma (HCC) cells. High level of DCP in serum and tissue is considered to show the malignant potential of HCC. In this paper, we described the proliferation and migration of human vascular endothelial cells by DCP. MTT assay showed that DCP could significantly stimulate HUVEC ECV304 cell proliferation with dose and time dependent manner. A continuous rapid migration of ECV304 cells was seen after treatment with DCP as measured by the scratch wound assay. A continuous rapid invasive activity as evaluated by transwell chamber assay also showed that DCP increased endothelial cells migration through the reconstituted extracellular matrix. The tube formation of vascular endothelial cells on 3-D Matrigel showed an increase of branch points of ECV304 cells exposed to DCP. The expressions of vascular endothelial cell growth-related angiogenic factors and matrix metalloproteinase were examined by Western blotting assay. DCP significantly stimulated the expression levels of epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-2 (latent and active). Together, these results suggest that DCP is a vascular endothelial growth factor. DCP may play a crucial role of mitogenic and migrative activities in angiogenesis in the development of HCC.

曲显俊、袁奕、李园园

肿瘤学基础医学生理学

肝细胞肝癌异常凝血酶原DCP人血管内皮细胞微血管形成EGFRVEGF基质金属蛋白酶MMPs

HCCDCPhuman vascular endothelial cellangiogenesisEGFRVEGFMMPs

曲显俊,袁奕,李园园.异常凝血酶原(DCP)促进人血管内皮细胞增殖与迁移作用研究[EB/OL].(2013-01-14)[2025-08-02].http://www.paper.edu.cn/releasepaper/content/201301-587.点此复制

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