利用协同效应逆向筛选中药中肿瘤多药耐药逆转剂

项目名称： 利用协同效应逆向筛选中药中肿瘤多药耐药逆转剂

项目编号： No.30801514

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 汪俊松

作者单位： 中国药科大学

项目金额： 20万元

中文摘要： 恶性肿瘤是一种威胁人类健康的重大疾病，肿瘤细胞对抗癌药物的多药耐药（MDR）是导致化疗失败的主要原因，也是困扰肿瘤临床治疗的关键性难题。我们认为，中药中应该存在自身不具有抗肿瘤活性但是能协同提高抗癌药物活性的物质存在，从抗肿瘤中药中试图分离有效抗癌物质的努力经常失败或得到的物质活性较弱可能正是因为忽视了这种协同效应的存在。基于这一认识，本项目充分利用多学科交叉的优势，结合中医药理论，以清热解毒和活血化淤类临床抗肿瘤中药为研究对象，以对细胞毒性、P-糖蛋白（P-gp） 调节、对细胞周期抑制和诱导细胞凋亡作用为指标，采取色谱分离和活性筛选相结合的方法，通过向受试样品中加入一定量已知抗癌药来逆向筛选肿瘤MDR 逆转剂。深人研究肿瘤MDR的中药逆转，对提高肿瘤化疗敏感性，进一步揭示肿瘤的耐药机理有重要临床意义和指导作用，也是合理开发利用中药的重要前提，有助于推动中药学科的发展。

中文关键词： 中药；肿瘤；多药耐药；逆转剂；P-糖蛋白

英文摘要： Malign tumor is a severe menace to human health. Currently the predominant mode of treatment for cancer patients is chemotherapy, but in many cases therapeutic efficacy is severely limited because of the tumor cells' multidrug resistance (MDR). It was suggested that the Traditional Chinese Medicine (TCM) should contain compounds which, while not active themselves, might work synergistically to enhance the activity of the natural anti-tumor agents. The frequent failures to isolate single active substances from TCM could be explained by synergistic interaction among different compounds. This program involves multidisciplinary cooperation and monitoring the potential of plant extracts of clinically used anticancer TCM herbs for "Clearing away Heat and Toxins", and herbs for "Promoting Blood Flow to Remove Stasis", selected based on the theory of TCM, to reverse tumor cell MDR. Chromatographical fractionation monitored by cytotoxic, P-gp modulating, cell cycle inhibitory and apoptosis inducing assays followed by spectroscopic analysis would characterize modulators of MDR tumor cells. A known antitumor agent will be added to each sample to retro-screen their reversal potential. Screening new reversal agents of cancer cell MDR from TCM could recover the tumor cell sensitivity to chemotherapy, further understand the mechanism of tumor cell MDR, which has clinical significance, lay the foundation of the rational utilization of TCM and help its development.

英文关键词： Traditional Chinese Medicine (TCM); tumor; multidrug resistance (MDR); reversal agents; P-gp