胶质瘤是脑内最常见的具有高复发率和高死亡率特点的原发性恶性肿瘤，目前尚缺乏有效的治疗方法。铁坏死是以细胞内二价铁离子增加以及二价铁离子依赖性的活性氧增加和脂质氧化损伤为特征的细胞死亡方式。我们发现，土槿皮乙酸（PAB）以及铁坏死诱导剂Erastin和RSL-3在诱导胶质瘤细胞铁坏死的同时还激活了STAT6（信号传导和转录激活因子6），抑制STAT6可以阻断二价铁离子增加以及脂质氧化损伤，并减少胶质瘤细胞死亡。因此，我们提出“STAT6促进了胶质瘤细胞铁坏死”的科学假说。在本项目中，我们采用体外和体内研究，应用生物化学和分子生物学方法探讨：（1）PAB对STAT6的激活作用及机制；（2）STAT6在胶质瘤细胞铁坏死中的作用；（3）STAT6调节二价铁离子增多的机制；（4）STAT6调节脂质氧化损伤的机制。我们期望通过本研究阐明STAT6在胶质瘤细胞铁坏死发生和发展中的作用及机制。

Gliomas are the common primary malignant tumors within brain tissue with higher mortality and recurrence. Currently, no effective treatment could be used for the patients with glioma. Ferroptosis is a newly-established cell death mode characterized by abnormally increased ferrous iron and overproduction of lipid hydroperoxide. We have found that Pseudolaric acid B (PAB) and other ferroptosis inducers not only induced glioma cell ferroptosis, but also activated STAT6. In contrast, inhibition of STAT6 with its specific inhibitor AS1517499 could abrogate PAB-induced cell death, increase of cellular ferrous iron, and lipid peroxidation. Thus, we speculate that STAT6 might be the upstream signal of ferroptosis. In this study, we used glioma cell culture in vitro and glioma model in vivo, and biochemical and molecular biological methods such as western blotting and enzyme activity assay to investigate the following issues: (1) How PAB activats STAT6 and its underlying mechanism; (2) The role of STAT6 in glioma cell ferroptosis; (3) The mechanism accounting for the regulatory effect of STAT6 on intracellular iron balance;(4) The mechanism responsible for the regulatory effect of STAT6 on the formation of lipid peroxide. We hope to clarify the role of STAT6 in glioma cell ferroptosis and its underlying mechanism via this study.