ARPP-19调控细胞周期促进肝癌细胞增殖及中药肝积方的干预

项目名称： ARPP-19调控细胞周期促进肝癌细胞增殖及中药肝积方的干预

项目编号： No.81202667

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 宋海燕

作者单位： 上海中医药大学

项目金额： 23万元

中文摘要： 肝细胞性肝癌（HCC）严重危害人类健康，目前诊疗措施仍不足以控制该疾病。抑制HCC细胞分裂增殖是重要治疗靶向。在前期小样本试验中发现环腺苷酸调节磷酸化蛋白-19（ARPP-19）在HCC组织表达升高，而近期报道该分子是进入分裂中期的关键调控分子。本单位据肝癌病机"脾虚为本，气滞血瘀、湿热、毒邪为标"组成中药肝积方，长期应用于临床可抑制肿瘤生长，有效延长肝癌患者生存期，但机制不明限制其推广应用。 基于此，本项目首先应用临床组织样本研究ARPP-19表达活化与HCC相关性；进而通过体外、体内HCC模型研究ARPP-19对HCC细胞周期、增殖、成瘤的影响及相关途径；同时基于ARPP-19调控细胞周期和增殖方面探讨肝积方治疗HCC的药效机制。 通过本项目有望揭示HCC发生发展新机制，增加HCC诊疗新靶标，为中医HCC辩证治则理论提供现代生物学释义，为肝积方治疗HCC的推广提供科学依据。

中文关键词： 肝细胞性肝癌；环腺苷酸调节的磷酸化蛋白-19；细胞增殖；细胞周期；肝积方

英文摘要： Hepatocellular carcinoma(HCC) still belongs to the most common malignancy affecting human health seriously, which challenges the development of efficient diagnosis and treatment measures urgently. One important therapeutic target is to inhibit HCC cell proliferation. Recent studies demonstrate that cAMP regulated phosphoprotein 19 (ARPP-19) play a pivotal role for cell mitosis G2/M transition. And overexpression of ARPP-19 in HCC was detected in our previous small sample experiment. Traditional Chinese medicine Ganji recipe has been used in clinic for a long term in Tumor Department of Longhua Hospital, with function of improving survival time of HCC patients, while the unclear underlying mechanisn limits the extending application. Therefore, this study will compare the expression and activity of ARPP-19 in human HCC and the adjacent tissues, to analyze the correlation with HCC. Then in vitro and in vivo experiments will be performed to investigate ARPP-19 function in HCC cell cycle control, proliferation regulation and tumorigenisis, as well as the signal pathway. In addition, Ganji recipe will be applied to in vivo HCC model to observe the intervening impact, and more significant, to explore the HCC-suppressing mechanism of Ganji recipe from the point of mitosis cell cycle regulation and proliferation. This st

英文关键词： Hepatocellular carcinoma；ARPP-19；Cell proliferation；Cell cycle；Ganji recipe