摘要
目的:筛选能够特异性抑制胶质瘤干细胞(GSC)增殖且已经应用于临床的小分子化合物,为脑肿瘤的靶向治疗提供线索。方法:用美国食品药品监督管理局(FDA)批准的药物库中640种小分子化合物药物处理GSC,并以人正常星形胶质细胞NHA作为对照,通过高内涵筛选出能够特异杀伤GSC的小分子抑制剂。用不同浓度的奥卡西平处理多株人胶质母细胞瘤患者来源的GSC细胞T3691、T3832、T387、T4121、D456以及正常星形胶质细胞NHA,在第4 d检测细胞相对生长活力,对比奥卡西平对不同细胞增殖的影响。结果:从FDA批准的小分子药物库中筛选到奥卡西平能够显著抑制GSC的增殖能力,且对NHA的生长影响不明显。奥卡西平在终浓度为5μmol/L时已经对多株GSC的增殖能力具有显著的抑制作用,并且在NHA中的IC50远高于GSC。结论:奥卡西平具有良好的抑制GSC增殖的能力,并且对NHA影响不显著,这为探索靶向治疗胶质瘤新方法提供了重要依据。
Objective:To screen the clinical applied small molecular inhibitors that can specifically inhibit the proliferation of glioma stem cells(GSC),providing potential strategies for targeting therapy of brain tumors.Methods:Treatment of 640 compounds from the FDA approved drug library to GSC and normal human astrocytes(NHA)with a final concentration of 10μmol/L.Screening small molecular inhibitors that can specifically kill GSC through high-content screening.The different concentration of oxcarbazepine was added to multiple glioblastoma-derived GSC,including T3691,T3832,T387,T4121 and D456,and human astrocytes NHA,and relative cell viability was assessed on day 4 to compare the effect of oxcarbazepine on cells proliferation.Results:Oxcarbazepine was identified from the FDA approved drug libraries that significantly inhibited the proliferation of GSC but had no significant effect on NHA.At the concentration of 5μmol/L,oxcarbazepine dramatically inhibited the proliferation of multiple GSC.The IC50 of oxcarbazepine in NHA was much higher than that in GSC.Conclusion:Oxcarbazepine specifically inhibits the proliferation of GSC,but spares NHA,providing an important basis for exploration of the new strategies of targeting therapy for glioma.
作者
刘召丹
陈丽树
满江红
LIU Zhao-Dan;CHEN Li-Shu;MAN Jiang-Hong(National Center for Biomedical Analysis,Beijing 100850,China)
出处
《生物技术通讯》
CAS
2020年第5期561-564,共4页
Letters in Biotechnology
基金
国家自然科学基金(81572889)。
