中文摘要
肿瘤干细胞是肿瘤发生发展、复发和转移的重要原因,应是肿瘤治疗的重要靶标。胶质母细胞瘤干细胞是能体外长期培养、且保持遗传学、生物学特性稳定的肿瘤干细胞,有利于药物筛选;胶质母细胞瘤恶性程度高、预后差,缺乏治疗药物。天然产物是抗肿瘤药物的重要源泉,相比植物总提物,其精制组分提高了有效成分的相对含量,提升了筛选命中率和发现活性化合物的可行性。.前期建立了抗肿瘤干细胞的筛选体系,以及符合人遗传学特征的胶质母细胞瘤动物模型。进一步筛选获得具有抗胶质母细胞瘤干细胞活性的云南特色药用植物有效组分100余个,显示出比现有活性化合物更多样的结构类型。.本项目拟研究资源植物有效组分库的化学成分,通过活性跟踪分离鉴定抗胶质母细胞瘤干细胞的活性化合物15-20个,完成其中1-2个重要分子的动物体内抗胶质母细胞瘤功能及其作用机制研究,以期发现治疗胶质母细胞瘤的新型先导分子。
英文摘要
Tumor stem cells (TSCs) are widely accepted as a main cause of tumor chemo -resistance and radio-resistance, tumor migration and recurrence, and consequently the ideal target of therapy. Glioblastoma stem cell is the only type of tumor stem cell that can be cultured in vitro and keep stable in biological characteristics, gene expression pattern and genomic integrity for long time. Glioblastoma is extremely malignant with bad prognosis and little therapies. Natural products and their derivatives are mains constituent in antitumor drugs, and their structures diversity play a very important role in new drugs discovery. We established tumor stem cell-based high content screening technology (HCS) and animal model better mimicking the cancer etiology. More than 7000 defined fractions from medicinal plants were prepared and were subject of Glioblastoma stem cell screening. As a result, more than 100 fractions were active. Now we are going to identify the diverse active molecules by bioassay-guided isolation from the active fractions. 15-20 active compounds should be isolated, and then, the mechanism and in vivo evaluation on glioblastoma of 1-2 promising candidates from screening will be finished. Hopefully, the lead compounds for glioblastoma therapy agents can be expected by this project.
