胶质母细胞瘤致死率很高，目前仍无理想治疗药物。我们在前期工作中从海绵Jaspis stellifera中分离得到抗癌活性物质STELB，该化合物以0.03μM的IC50抑制胶质母细胞瘤SF295细胞的增殖，且对多种正常细胞未显示毒性（IC50>10μM）。进一步研究表明STELB可诱导SF295细胞凋亡和自噬，且与抑制PI3K催化亚基p110的表达及下游Akt等的磷酸化有关。本课题拟利用胶质母细胞瘤细胞SF295和U251，深入研究STELB单独给药及与临床一线药物替莫唑胺联合使用的体外和体内抗胶质母细胞瘤的作用；还将利用基于生物信息学的JFCR39药物靶点发现系统以及基于化学蛋白质组学的生物素标记小分子探针和蛋白质分离分析技术研究STELB的分子靶点，并在酶水平和细胞水平对分子靶点进行验证，从而阐明STELB抑制胶质母细胞瘤的分子机理，为研发此类新型抗肿瘤药物提供理论依据和实验基础。

Glioblastoma remains to be one of the most lethal cancers. Presently, there is no drug with satisfying efficacy for glioblastoma therapy. Recently, we isolated STELB (stellettin B) from marine sponge Jaspis stellifera. STELB inhibits the proliferation of glioblastoma cell SF295 with an IC50 of 0.03 μM while showing very weak cytotoxicity to several normal cell lines (IC50 > 10 μM). Our further study indicated that STELB induced apoptosis and autophagy in SF295 cells, which might be attributed to blocking expression of PI3K catalytic subunit p110 and therefore the phosphorylation of downstream effectors like Akt, mTOR, etc. However, the direct molecular target as well as the detailed mechanism remains unclear yet. With the support of NSFC grant, we will investigate the antitumor activity of STELB on glioblastoma in vitro and in vivo by use of SF295 and U251 cells. Furthermore, we will investigate the combinational effect of STELB and temozolomide which is used in clinic as the first-line drug. Finally, we will try to elucidate the molecular target as well as the mechanism of STELB for the anti-glioblastoma effect, by utilizing bioinformatic JFCR39 drug-target-discovery system and biotin-labeled STELB based on chemical proteomics. To confirm the target, enzyme-based bioassay such as Adapta, and cell signal pathway study will be carried out. After finishing this project, we would be able to demonstrate the anti-glioblastoma efficacy of STELB and provide the target information for such type of antitumor drugs, therefore contributing to glioblastoma therapy in the future.