逆转P-gp介导的骨肉瘤细胞多药耐药性作用中药的筛选及其机制研究

项目名称： 逆转P-gp介导的骨肉瘤细胞多药耐药性作用中药的筛选及其机制研究

项目编号： No.81202901

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： 杨蕾

作者单位： 中国药科大学

项目金额： 22万元

中文摘要： 骨肉瘤是最常见的恶性骨肿瘤，儿童和青少年多发，致残率和致死率极高、预后极差。目前的治疗主要以手术、化疗为主。骨肉瘤细胞对化疗药物的耐受，特别是交叉耐受是导致患者化疗失败的主要原因。因此，逆转骨肉瘤多药耐药的研究已逐渐成为研究热点。我国传统中医药学对骨肿瘤的治疗始于周代，活血化瘀、益气健脾是中医内治恶性骨肿瘤的基本配伍规律，并根据临床辨证辅以清热解毒、化湿、化痰、补肾等。本项目在前期研究工作的基础上，以活血、清热和化湿等中药为研究对象，采用色谱分离和活性筛选相结合的方法，检测待测组分在耐药骨肉瘤细胞模型上的逆转倍数，对阿霉素蓄积的影响，对P-gp蛋白功能和表达的影响，筛得活性成分。利用基因工程技术建立P-gp单因素耐药的人骨肉瘤细胞MG-63/MDR1模型，进一步确定P-gp作用底物。本项目为从中药中发现高效低毒、结构新颖具有药用价值的活性化合物，阐明其作用机理，开发新型肿瘤逆转剂奠定基础。

中文关键词： 多药耐药；骨肉瘤；P糖蛋白；阿霉素；中药

英文摘要： Osteosarcoma is the most common malignant tumor of bone, frequently occurred in children and adolescents. Chemotherapy and surgical resection are two major treatments of osteosarcoma. Surgical resection leads to handicap of patients, which made chemotherapy the more favorable. However, 30-40% patients still suffer local recurrence or metastasis, due to the development of multidrug resistance (MDR). Traditional Chinese medicine (TCM) has long history documentation on bone tumors therapy. The basic treatment rules in TCM are nourishing qi to invigorate spleen and promoting blood flow, combining with dissipating phlegm, dehygrosis or heat-clearing, and detoxicating according to clinic syndromes. On the basis of preliminary study, this project focuses on screening reversal agents of MDR from TCMs. Fractionated extracts and compounds from traditional medicine would be tested for their potential to modulate the MDR phenotype and function of P-gp in MG-63/ADR cells in vitro. P-gp single factor multidrug resistance model (MG-63/MDR1 cells) is about to be established for finding the inhibitors of P-gp from them. The results of this project will afford some useful MDR-reversing agents, giving a glimpse of the therapeutic value of TCM in this regards.

英文关键词： Multidrug resistance；osteosarcoma；P-glycoprotein；Doxorubicin；traditional Chinese medicine