Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. lpyalexandra @ gmail.com
Oncology. 2013;84(6):326-35. doi: 10.1159/000347021. Epub 2013 Apr 27.
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（GBM）是最常见和侵袭性最强的原发性脑肿瘤之一。在完全手术切除联合放疗和化疗后，约 10%的患者能存活 5 年以上。因此，需要一种新的 GBM 治疗方法。Aurora-A（AURKA）在细胞周期调控中发挥重要作用，如中心体成熟、染色体分离、双极纺锤体组装和有丝分裂进入。为了研究 AURKA 抑制的效果，用 Aurora-A 抑制剂 VE-465 处理三种 GBM 细胞系，包括 GBM 8401、GBM 8901 和 U87-MG 细胞。GBM 8401、GBM 8901 和 U87-MG 细胞的 50%抑制浓度值（IC50）分别为 6、25 和 19 nM，表明对 VE-465 的敏感性。此外，VE-465 处理后 GBM 8401 和 GBM 8901 细胞的集落形成减少。VE-465 处理以 caspase 非依赖性方式增加多倍体和 p53 蛋白表达，并抑制细胞生长。总之，这些结果表明，小分子抑制剂抑制 AURKA 可能成为 GBM 的一种新的治疗方法。
