Clinic for Neurosurgery, Medical Faculty, Heinrich-Heine University Düsseldorf, 40225, Germany.
Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100050, PR China.
CNS Oncol. 2020 Jun;9(2):CNS58. doi: 10.2217/cns-2020-0004. Epub 2020 May 28.
Glioblastoma is a heterogeneous lethal disease, regulated by a stem-cell hierarchy and the neurotransmitter microenvironment. The identification of chemotherapies targeting individual cancer stem cells is a clinical need. A robotic workstation was programmed to perform a drug concentration to cell-growth analysis on an model of glioblastoma stem cells (GSCs). Mode-of-action analysis of the selected top substance was performed with manual repetition assays and acquisition of further parameters. We identified 22 therapeutic potential substances. Three suggested a repurpose potential of neurotransmitter signal-modulating agents to target GSCs, out of which the Parkinson's therapeutic trihexyphenidyl was most effective. Manual repetition assays and initial mode of action characterization revealed suppression of cell proliferation, cell cycle and survival. Anti-neurotransmitter signaling directed therapy has potential to target GSCs. We established a drug testing facility that is able to define a mid-scale chemo responsome of cancer models, possibly also suitable for other cell systems.
胶质母细胞瘤是一种异质性致死性疾病,由干细胞层次结构和神经递质微环境调控。鉴定针对个别肿瘤干细胞的化疗药物是一种临床需求。一个机器人工作站被编程为对胶质母细胞瘤干细胞(GSCs)模型进行药物浓度与细胞生长分析。通过手动重复实验和获取进一步的参数,对选定的最佳物质进行作用模式分析。我们确定了 22 种有治疗潜力的物质。三种提示神经递质信号调节剂有重新定位以靶向 GSCs 的潜力,其中帕金森病治疗药物三己苯并嘧啶最为有效。手动重复实验和初始作用模式特征揭示了对细胞增殖、细胞周期和存活的抑制作用。靶向 GSCs 的神经递质信号抗传递治疗具有潜力。我们建立了一个药物测试设施,能够定义癌症模型的中等规模化疗反应组,也可能适用于其他细胞系统。