天然产物是药物的主要来源，而海洋天然产物具有更大的成药性。我们前期发现海洋微生物产生的浅蓝霉素类生物碱具有细胞和体内的抗人结直肠癌活性。本项目拟在此基础上，通过微生物发酵发掘浅蓝霉素类生物碱的化学多样性；在细胞和分子水平上评价其对人结直肠癌细胞及其干细胞P6C的抑制作用，进而探讨其对拓扑异构酶IIα(Topo IIα)、人结直肠癌干细胞P6C的细胞周期、细胞凋亡及其相关信号通路的影响，为发现靶向肿瘤干细胞的抗人结直肠癌新药提供科学依据。

Natural products (NPs) are the main sorce of the new drugs, of which marine natural products (MNPs) showed better druggability than terrestrial NPs. Our previous study revealed that the cerulomycins sorced from a marine microorganism showed good effects against colorectal cancer (CRC) both in vitro and in vivo. In this project, the chemodiversity of cerulomycins will be explored by microbial fermentation. Then, the cytotoxicity against CRC cells and CRC stem cell (P6C) will be assayed. Furthermore, the effects of cerulomycins on topoisomerase IIα (Topo IIα), cell cycle and apoptosis as well as their related signaling pathway of P6C stem cell will also be investigated. The results are expected to provide scientific evidences for the discovery of the new anti-CRC drugs targeted tumor stem cell.