胶质母细胞瘤（GBM）是众所周知的预后性极差的中枢神经系统恶性肿瘤。研究发现，青蒿素类不仅能够用于疟疾治疗还具有抗肿瘤作用，能通过抑制GPX4诱导肿瘤铁死亡而增加化疗敏感性，但其在GBM中的作用不清楚。我们前期发现，CD44v、xCT和GPX4表达在GBM中显著增高；抑制xCT或GPX4活性能阻碍GBM细胞合成谷胱甘肽，引发活性氧自由基积累和铁死亡，进而化疗增敏和血管新生抑制；另外，青蒿琥酯通过抑制xCT活性诱导GBM细胞铁死亡。因此，我们推测：青蒿素类能通过调控CD44v/xCT/GPX4通路而抑制GBM发生发展。我们拟建立原代GBM细胞、化疗诱导的GBM细胞和GBM荷瘤裸鼠模型，实时动态分析CD44v/xCT/GPX4通路在GBM生长、抑制铁死亡和耐药性中的作用机制，明确铁死亡与肿瘤耐药性和血管生成的关系，揭示青蒿素类通过抑制CD44v/xCT/GPX4通路诱导GBM铁死亡的分子机制。

It is well-known that glioblastoma (abbreviated as GBM) is the most lethal central nervous system tumor. Artemisinins can not only be used for the treatment of malaria, but also has anti-tumor effect. Studies showed that artemisinins can induce ferroptosis in some tumors by inhibiting GPX4 activity, and then increase chemosensitivity. However, the mechanisms and the effect of artemisinins in GBM are not clear. We found that GBM showed increasing signs of malignancy induced by concomitant CD44v, xCT and GPX4 expression. Conversely, xCT or GPX4 activity inhibition could decrease intracelluar gluathione, induce accumulation of intracellular reactive oxygen species and subsequent ferroptosis. Further, we found artesunate could induce ferroptosis in GBM cells through inhibiting xCT activity. So, we propose that artemisinin can inhibit the development of GBM by regulating the CD44v/xCT/GPX4 pathway. We aim to establish the primary GBM cells, chemotherapy-induced GBM cells and GBM tumor-bearing nude mice models. Based on these models, we will dynamically observe and analyze the mechanism of CD44v/xCT/GPX4 pathway in GBM growth, process of induced-ferroptosis and drug resistance. Ferroptosis on tumor drug resistance and angiogenesis will be revealed. We will provide the understanding of the molecular mechanism of artemisinins in inducing ferroptosis in GBM via CD44v/xCT/GPX4 pathway.