蟾毒灵靶向糖酵解途径抗STRO1+/CD117+骨肉瘤肿瘤干细胞机制研究

项目名称： 蟾毒灵靶向糖酵解途径抗STRO1+/CD117+骨肉瘤肿瘤干细胞机制研究

项目编号： No.81472506

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 沈靖南

作者单位： 中山大学

项目金额： 72万元

中文摘要： 骨肉瘤是青少年最常见原发恶性骨肿瘤，复发、转移仍是当前临床治疗难题。近年来研究表明肿瘤干细胞是肿瘤复发及转移的根源。我们前期研究发现蟾毒灵对STRO-1/+CD117+骨肉瘤肿瘤干细胞具有显著杀灭效果，进一步通过蛋白质组学筛查证实蟾毒灵处理后胞内糖酵解途径关键酶α烯醇化酶（Enolase1）和磷酸丙糖异构酶-1（TPI1）表达明显下调，然而目前糖酵解在蟾毒灵抗骨肉瘤肿瘤干细胞中的作用及其机制尚未阐明。现拟在前期基础上利用多种细胞、动物模型验证蟾毒灵体内外抗骨肉瘤肿瘤干细胞的作用；检测细胞耗氧量、糖酵解指数等能量代谢指标，探索糖酵解关键酶Enolase1、TPI1作为抗骨肉瘤肿瘤干细胞治疗靶点的价值；通过转染、干扰等方法阐明糖酵解途径在蟾毒灵抗骨肉瘤肿瘤干细胞中的意义。本项目将深化对蟾毒灵抗骨肉瘤肿瘤干细胞的认识，揭示糖酵解途径在蟾毒灵抗骨肉瘤肿瘤干细胞中的作用，为骨肉瘤治疗提供新的策略。

中文关键词： C18_骨肿瘤；骨肉瘤；蟾毒灵；糖酵解；肿瘤干细胞

英文摘要： Osteosarcoma is the most common primary malignant bone tumor in adolesent, the recurrence and metastasis still challenge the oncologists. Recently, numerous researches demonstrate that the tumor stem cell is the origin of recurrence and metastasis. Our preliminary data showed bufalin possessed a strong anti-tumor effect on STRO-1+CD117+ osteosarcoma stem cell.Further,we found TPI1 and Enolase 1, the key enzymes in glycolysis, were significantly down-regulated following bufalin treatment,however,the molecular mechanism and the in vivo the anti-tumor stem cell effect of bufalin is still unclear. Therefore, the present study will use more cell lines and animal model to validate the anti-tumor stem cells effect in vitro and in vivo; detect the index of glycosis and combining with the clinical data to assess the value of TPI1 and Enolase 1 as the therapeutic targets; employ variety of biological assays to elucidate the mechanism of bufalin anti-tumor stem cell effect. This study will deepen the knowledgement of the bufalin anti-tumor stem cell effect,elucidate the importance of glycosis in the treatment of osteosarcoma and provide a new therapeutic strategy of osteosarcoma.

英文关键词： bone tumor;osteosarcoma;bufalin;glycolysis;tumor stem cell