胶质瘤耐药是治疗失败的重要原因之一。抗癫痫药物(AEDs)在胶质瘤患者的使用非常普遍，选择合适的抗癫痫药物，如果既可治疗/预防癫痫，又能化疗增敏，一举两得。我们前期研究发现：①左乙拉西坦（LEV）、丙戊酸钠（VPA）等AEDs在部分胶质瘤可增敏一线化疗药替莫唑胺（TMZ）；②干扰素(IFN)可抑制NF-κB活性，下调MGMT表达，从而逆转TMZ耐药。提示，AEDs-IFN-TMZ三药联用有望最大化增加胶质瘤疗效，而目前国内外尚无报道。我们推测AEDs-IFN-TMZ鸡尾酒式疗法可抑制NF-κB活性，继而下调MGMT表达，以及促进凋亡和自噬性死亡，增强TMZ对胶质瘤的杀伤效应。本研究旨在明确鸡尾酒式(AEDs-IFN-TMZ)化疗方案的疗效，揭示相关分子机制，并探讨针对胶质瘤的不同分子特征选用不同AEDs联合的分子生物学依据，为胶质瘤精准治疗方案的制订提供实验依据。

Drug resistance is one of the most important reasons for glioma treatment failure. The application of anti-epileptic drugs (AEDs) are widly used in glioma. It will be very recommendable if AEDs could both anti-/prevent epileptic and enhance chemotherapy effect. Our previous studies have found that: 1) AEDs, such as Levetiracetam (LEV) and Valproic acid(VPA), could sensitize the efficacy of TMZ, a first line chemotherapeutic drug for glioma. 2) Interferon (IFN) could reverse the resistance of TMZ by inhibiting NF-κB activity, down-regulating the expression of MGMT. Our preliminary data indicated that the combination of AEDs-IFN-TMZ could improve the treatment efficiency of glioma dramatically, which has never been reported. Our hypothesis is that the cocktail strategy, AEDs-IFN-TMZ, could attenuate the activity of NF-κB, downregulate expression of MGMT afterwards, and induce apoptosis and autophagy, therefore promote the killing effect of TMZ. This proposal aim to confirm the effects of this sequential treatment strategy with cocktail medication, investigate the related molecular mechanisms, set up the standards for choosing proper AEDs for patients with different molecular characteristic backgrounds. This work will provide the experimental basis for the personalized glioma treatment.