多形性胶质母细胞瘤（GBM）是最常见的原发性中枢神经系统恶性肿瘤，预后差。坏死形成是GBM的重要组织学特征，坏死的出现及其严重程度可以预测GBM的不良预后，但坏死形成的机制尚未明确。我们前期实验证实，活化T细胞核因子1（NFAT1）在GBM中的表达显著升高，当处于普通活化状态时，其促进细胞侵袭；而当NFAT1过度激活时，则通过“活化诱导的细胞死亡”样作用导致细胞死亡。GBM组织中存在引起NFAT1过激活的因素，如局部低氧等，结合文献报道NFAT1对坏死的调控,我们推测，在局部低氧环境下，NFAT1可能通过与HIF-1、TNF-α协同作用，诱导GBM坏死形成。本研究旨在通过调控肿瘤中NFAT1的表达及活性，建立动物模型，结合体外实验，探讨NFAT1在GBM坏死形成中的作用及分子机制，进而完善GBM恶性进展的内在机制，为GBM靶向治疗提供新的靶点，为诱导GBM由坏死向凋亡转化提供新的思路。

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor, and patients confront an extremely poor clinical outcome. Among the histological hallmarks of GBM, necrosis has been demonstrated to be a powerful predictor of poor patient prognosis. Although hypoxia and the expression of Hypoxia-induced Factor-1 (HIF-1) and Tumor Necrosis Factor-α (TNF-α) have been reported to play a role in the formation of necrosis, the mechanism of the development of necrosis in GBM remains unclear. In our previous studies, we found that the expression and activity of the nuclear factor of activated T cells-1 (NFAT1) are significantly up-regulated in GBMs. Importantly, activation-induced cell-death-like phenomena can occur in GBM cells when NFAT1 are over-activated. It has been reported that hypoxia could increase NFAT1 activation in GBM cells. Moreover, as a transcriptional factor, NFAT1 can regulate the expression of HIF-1 and TNF-α. In addition, under certain circumstances NFAT1 can induce necrosis. Therefore, we speculate that under hypoxic condition, by interaction with HIF-1 and TNF-α, NFAT1 may participate in the necrosis formation of GBMs. In the present study, using the stable transfection method to regulate the activity of NFAT1 and by the establishment of animal model in combination with in vitro experiments, we aimed to investigate the role of NFAT1 in the necrosis formation of GBM and the related molecular mechanism, which would contribute to the understanding of the mechanism of GBM malignant progression. The results of the study would provide new molecular targets for the treatment of GBM.