脑胶质瘤是颅内最常见的具有高复发率和高死亡率特点的恶性肿瘤，目前缺乏有效的治疗方法。Parthanatos是以PARP-1过度激活和细胞中PAR积聚为特征的程序性死亡方式。我们发现，脱氧鬼臼毒素（DPT）在体外和体内均能诱导胶质瘤细胞Parthanatos，抑制JNK或P38均可以减少DPT诱导的胶质瘤细胞死亡，进而提出科学假说“JNK/P38MAPK调节了胶质瘤细胞的Parthanatos”。在本项目中，我们采用体外和体内研究，应用免疫沉降、蛋白印迹等方法探讨：（1）DPT激活JNK/P38的机制；（2）JNK/P38在DPT诱导胶质瘤细胞Parthanatos中的作用；（3）JNK/P38调节PARP-1过度激活的机制；（4）JNK/P38对PARG（PAR降解酶）的影响及机制。我们期望通过本研究阐明JNK/P38MAPK对胶质瘤细胞Parthanatos的调节作用和机制。

Gliomas are the common malignant intracranial primary tumors with higher mortality, higher recurrence and no effective treatment. Parthanatos is a type of programmed cell death characterized with PARP-1 hyper-activation and cytoplasm accumulation of PAR. Different with improving the sensitivities of glioma cells to current chemotherapy and radiotherapy by inhibition of PARP-1 activation, induction of parthanatos might become a new strategy to eliminate glioma cells in further. We found that deoxypodophyllotoxin (DPT) could induce glioma cell parthanatos in vitro and in vivo, in which JNK/P38MAPK might play a crucial role. Thus, we hypothesize that JNK/P38 MAPK might participate in the regulation glioma cell parthanatos induced by DPT. In this research project, we will use various glioma cell lines and naked mice model of xenograft glioma, and molecular biology technologies such as western blotting analysis and immunoprecipitation to investigate the following issues: (1) The effect of JNK/P38 MAPK on the glioma cell parthanatos triggered by DPT; (2) The mechanism underlying the activation of JNK/P38 MAPK caused by DPT; (3) The mechanism via which JNK/P38MAPK regulate PARP-1 hyper-activation; (4) The effect of JNK/P38 MAPK on PARG and its underlying mechanism. We hope to clarify the role of JNK/P38 MAPK in glioma cell parthanatos and its potential mechanism, and present theoretical basis for developing corresponding treatment targeting parthanatos induction.