Supplementary Material for: The Aurora Kinases Inhibitor VE-465 is a Novel Treatment for Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is one of the most common and aggressive types of primary brain tumor. After complete surgical resection combined with radiation and chemotherapy, approximately 10% of patients survive for more than 5 years. Therefore, a novel therapy for GBM is needed. Aurora-A (AURKA) plays important roles in cell cycle regulation, such as centrosome maturation, chromatic separation, bipolar spindle assembly, and mitotic entry. To investigate the effects of AURKA inhibition, three GBM cell lines, including GBM 8401, GBM 8901, and U87-MG cells, were treated with the AURKA inhibitor VE-465. Sensitivities to VE-465, as indicated by 50% inhibitory concentration values for GBM 8401, GBM 8901, and U87-MG cells, were 6, 25, and 19 nM, respectively. Additionally, colony formation of GBM 8401 and GBM 8901 cells was decreased after treatment with the VE-465. VE-465 treatment increased polyploidy and p53 protein expression, and inhibited cell growth in a caspase-independent manner. Taken together, these results suggest that the inhibition of AURKA by a small-molecule inhibitor may have potential to serve as a novel therapeutic approach for GBM.

多形性胶质母细胞瘤（Glioblastoma multiforme, GBM）是最常见且恶性程度最高的原发性脑肿瘤之一。经根治性手术切除联合放化疗后，仅约10%的患者生存期可超过5年，因此亟需开发针对GBM的新型治疗手段。极光激酶A（Aurora-A, AURKA）在细胞周期调控中发挥关键作用，涵盖中心体成熟、染色体分离、双极纺锤体组装及有丝分裂启动等过程。为探究AURKA抑制的生物学效应，研究人员采用AURKA抑制剂VE-465处理了GBM 8401、GBM 8901及U87-MG这3种GBM细胞系。以半数抑制浓度（IC50）为评价指标，GBM 8401、GBM 8901和U87-MG细胞对VE-465的敏感性分别为6 nM、25 nM和19 nM。此外，经VE-465处理后，GBM 8401与GBM 8901细胞的集落形成能力显著下降。VE-465处理可诱导细胞多倍体化并上调p53蛋白表达，且以不依赖半胱氨酸天冬氨酸蛋白酶（caspase）的途径抑制细胞增殖。综上，上述结果表明，小分子抑制剂靶向抑制AURKA有望成为GBM的新型潜在治疗策略。