CSP I-plus 修饰的内皮抑制素靶向抑制肝细胞癌转移的研究

项目名称： CSP I-plus 修饰的内皮抑制素靶向抑制肝细胞癌转移的研究

项目编号： No.81502520

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 马艳

作者单位： 广东药科大学

项目金额： 18万元

中文摘要： 肝细胞癌（HCC）转移是导致患者死亡重要因素，抑制HCC 转移是提高患者预后重要措施。内皮抑制素（ES）抑制血管形成和癌细胞的迁移。疟原虫环子孢子蛋白CSP I-plus 能特异性与肝细胞表面硫酸乙酰肝素蛋白聚糖（HSPG）结合，HSPG参与调节肿瘤血管形成和转移。我们前期在成功构建ES 和CSP I-plus 融合蛋白（rES-CSP）的基础上发现：该融合蛋白除了能抑制血管形成，也能与肝癌HepG2细胞结合，抑制HepG2 迁移。血管形成和细胞迁移在肿瘤转移中扮演了重要的角色，据此我们感兴趣的问题是：①rES-CSP是否能靶向性抑制HCC 转移？②如果是，其机制又如何？本项目拟进一步研究：一方面从体内和体外确定rES-CSP靶向性抑制HCC转移的作用；另一方面探讨其靶向性及抗转移的机制。项目的实施将为阻断肝癌转移靶向治疗提供实验依据与药物开发思路。

中文关键词： 肝细胞癌；；；内皮抑制素；；肝靶向肽；肿瘤转移

英文摘要： Metastasis is an major obstacle for the survival of patients with hepatocellular carcinoma(HCC). Inhibiting metastasis of HCC is important to improve the prognosis of patients. Endostatin inhibits angiogenesis and cancer cell migration and adhesion. CSP I-plus, circumsporozoite protein of Plasmodium sporozoite binds with the sulfated heparan sulfate proteoglycan(HSPG) in the surface of liver cells specificly, Our previous work constructed the fusion protein, which contains the liver-targeting peptide CSP I-plus and recombinant human endostatin, not only inhibit angiogenesis, but also bind with HepG2 hepatoma cells and inhibit the migration of HepG2. Angiogenesis and cell migration play an important role in tumor metastasis. Our interest is: ①Whether rES-CSP targeted inhibiting metastasis of HCC? ② If yes, how about the mechanism? In this study, In this study, firstly we will research the targeting and mechanism of rES-CSP to hepatoma cells in vitro and in vivo. Then the impact of rES-CSP on the migration, adhesion of hepatoma cell MHCC97H and metastasis in orthotopic tumor will be identified. Finally the underlying mechanism will be clarified though in vivo and in vitro experiments.This study will provide new experimental evidence and drug development ideas for the targeted treatment of HCC metastasis.

英文关键词： hepatocellular carcinoma;Endostatin;liver-targeting peptide ;tumor metastasis