Inhibition of HDAC1/2 along with TRAP1 causes Synthetic Lethality in Glioblastoma Model Systems

Pan and selective HDAC inhibition is synthetically lethal with TRAP1 inhibition in various model systems of glioblastoma, including patient derived xenograft (PDX) cells. Mechanistically, this occurs through several mechanisms, including the induction of metabolic stress by interference with tumor cell energy metabolism accompanied by modulation of pro- and anti-apoptotic Bcl-2 family proteins and the induction of a cell death with apoptotic features. Overall design: Compared OXPHOs complex (SHDA and SDHB) level between U87 and U87PbR

在包括患者来源异种移植（PDX）细胞在内的多种胶质母细胞瘤模型系统中，广谱组蛋白去乙酰化酶（HDAC）抑制与选择性HDAC抑制联合TRAP1抑制可产生合成致死效应。
从机制层面而言，该效应的实现涉及多种途径：通过干扰肿瘤细胞能量代谢诱导代谢应激，同时调控促凋亡与抗凋亡Bcl-2家族蛋白，并诱导产生具有凋亡特征的细胞死亡。
实验整体设计：比较U87细胞与U87PbR细胞中氧化磷酸化复合物（OXPHOs）（SHDA与SDHB）的表达水平。