PTEN-PI3K/Akt细胞信号传导通路与美罗华单抗耐药的关系和机制研究

项目名称： PTEN-PI3K/Akt细胞信号传导通路与美罗华单抗耐药的关系和机制研究

项目编号： No.81201793

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1

项目作者： 吴晶晶

作者单位： 郑州大学

项目金额： 23万元

中文摘要： 美罗华对非霍奇金淋巴瘤单药治疗或联合化疗目前在世界范围被认为是最成功的生物治疗方式之一，但经过长期治疗后发现约半数以上病人可产生耐药。目前对于美罗华单抗耐药机制和耐药逆转方法的探索尚处于初步阶段。PTEN作为一种新的肿瘤抑制基因通过抑制其下游PI3K/AKT信号转导通路在肿瘤生长抑制、诱导凋亡、逆转耐药等多方面发挥重要的作用。本课题拟通过：1）检测CD20+ B细胞淋巴瘤患者使用美罗华后复发或有效时肿瘤组织内PTEN表达情况和PIK3CA突变情况，分析二者与美罗华耐药的关系；2）体外细胞实验研究PTEN-PI3K/Akt信号通路在美罗华耐药中的作用及机制；3）构建美罗华耐药的淋巴瘤小鼠模型，通过体内动物实验进一步验证PTEN-PI3K/Akt信号通路在美罗华耐药中的作用，为探索美罗华耐药机制和逆转美罗华耐药提供理论基础，同时有希望发现新的能够预测美罗华单抗疗效的生物学指标。

中文关键词： 美罗华耐药；PTEN；PI3K/Akt；淋巴瘤；细胞凋亡

英文摘要： The rituximab can justiably be described as the most effective, successful, and widely used therapeutic monoclonal antibody for non-Hodgkin lymphoma (NHL) developed to date. Nonetheless, as with any antineoplastic agent, the effectiveness of rituximab is ultimately limited in part by the development of treatment resistance. Despite wide-spread clinical use, the mechanisms by which tumor cells resist rituximab-mediated destruction remain unclear. PTEN , as a new tumor suppressor gene, can exert its tumor suppression effect through suppress PI3K/Akt pathway. 1) We propose to evaluate the association between PTEN and PIK3CA with efficacy of rituximab therapy in non-Hodgkin lymphoma by detecting the expression levels of PTEN and PIK3CA mutations in lymphoma tissues treated with rituximab effectively or ineffectively. 2) At the same time, we design to study the expression levels of PTEN and relevant target factors in the PI3K/Akt pathway in lymphoma cells resistant to rituximab to explore the mechanism of rituximab resistance in vitro. 3) Furthermore, we plan to study the role of PTEN-PI3K/Akt pathway in the rituximab resistance by establishing the model of rituximab-resistant lymphoma mouse in vivo. This study aims to provide a basic theory on rituximab resistance and find a new marker to predicate the effectiveness

英文关键词： Rituximab resistance；PTEN；PI3K/Akt；lymphoma；cell apoptosis