胶质母细胞瘤是临床最常见的恶性脑肿瘤，严重危害人类身体健康。在前期研究中，我们发现抗肿瘤药物瑞格菲尼对胶质母细胞瘤具有显著的抗肿瘤活性。进一步研究表明瑞格菲尼诱导胶质母细胞瘤细胞发生自噬。运用蛋白质组学技术结合生物信息学分析，我们发现瑞格菲尼可导致丝氨酸生物合成限速酶PSAT1表达异常。在此基础上，本项目拟阐明瑞格菲尼通过调控PSAT1激活胶质母细胞瘤细胞自噬的分子机制和信号调控网络，通过体内外实验明确自噬在瑞格菲尼抗胶质母细胞瘤中的生物学功能，评价干预自噬对瑞格菲尼抗胶质母细胞瘤效果的影响。本项目的实施有助于进一步阐明胶质母细胞瘤应对化疗的分子应答机制，为开发胶质母细胞瘤潜在治疗药物以及探寻新型治疗策略提供新思路。

Glioblastoma is the most common brain cancer which causes global health burden. Our preliminary work showed regorafenib could significantly inhibit glioblastoma cell growth. In addition, we demonstrated that regorafenib could stimulate autophagy in glioblastoma cells. Proteomics data suggest that Regorafenib caused aberrant expression of PSAT1 (phosphoserine aminotransferase 1), which is a rate-limiting enzyme in serine biosynthesis. In this project, we will clarify the molecular mechanisms underlying regorafenib-induced autophagy through regulating PSAT1 in glioblastoma cells. Moreover, we will evaluate the biological role of autophagy in regorafenib-inhibited glioblastoma both in vitro and in vivo. Our study will provide new insight into the cellular response mechanism of glioblastoma against chemotherapy, and pave the road for development of potential drugs or therapeutic strategies in glioblastoma treatment.