Abstract

Glioblastoma (GBM) is the most prevalent malignant tumour of the central nervous system and carries a poor prognosis; average survival time after diagnosis is 14 months. Because of its unfavourable prognosis, novel therapies are needed. The aim of this study was to assess whether inhibition of GBM and GBM-derived cancer stem cells (CSCs) by a new tyrosine kinase inhibitor (TKI), K905-0266, is possible. To do this, we generated GBM (D54 and U87MG) cells expressing luciferase and characterised the inhibitory effects of the TKI with bioluminescent imaging (BLI) and western blot (WB). The effect of the TKI was then evaluated in CSCs. BLI showed significant inhibition of D54 and U87MG cells by TKI treatment. WB showed that the TKI decreased pERK and Bcl-2 level and increased cleaved caspase-3 level. Sphere formation was significantly reduced by the TKI in CSCs. Our results showed that a new TKI, K905-0266, effectively inhibited GBM and CSCs, making this a candidate for GBM therapy.

摘要

胶质母细胞瘤（GBM）是中枢神经系统最常见的恶性肿瘤，预后较差；诊断后的平均生存时间为 14 个月。由于其不利的预后，需要新的疗法。本研究的目的是评估新的酪氨酸激酶抑制剂 (TKI) K905-0266 是否可能抑制 GBM 和 GBM 衍生的癌症干细胞 (CSC)。为此，我们生成了表达荧光素酶的 GBM（D54 和 U87MG）细胞，并用生物发光成像 (BLI) 和蛋白质印迹 (WB) 表征了 TKI 的抑制作用。然后在 CSC 中评估 TKI 的效果。BLI 显示 TKI 处理显着抑制 D54 和 U87MG 细胞。WB 显示 TKI 降低了 pERK 和 Bcl-2 水平，并增加了裂解的 caspase-3 水平。在 CSC 中，TKI 显着减少了球体形成。我们的结果表明，一种新的 TKI，K905-0266，可有效抑制 GBM 和 CSC，使其成为 GBM 治疗的候选者。