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通过抑制发动蛋白2功能靶向胶质瘤干细胞:胶质母细胞瘤的一种新治疗策略

Targeting Glioma Stem Cells by Functional Inhibition of Dynamin 2: A Novel Treatment Strategy for Glioblastoma.

作者信息

Luwor Rodney, Morokoff Andrew P, Amiridis Stephanie, D'Abaco Giovanna, Paradiso Lucia, Stylli Stanley S, Nguyen Hong P T, Tarleton Mark, Young Kelly A, O'Brien Terence J, Robinson Phillip J, Chircop Megan, McCluskey Adam, Jones Nigel C

机构信息

a Department of Surgery , The University of Melbourne, The Royal Melbourne Hospital , Parkville , Australia.

b Department of Neurosurgery , The Royal Melbourne Hospital , Parkville , Australia.

出版信息

Cancer Invest. 2019;37(3):144-155. doi: 10.1080/07357907.2019.1582060. Epub 2019 Mar 25.

DOI:10.1080/07357907.2019.1582060
PMID:30907150
Abstract

Glioma stem cells (GSCs) play major roles in drug resistance, tumour maintenance and recurrence of glioblastoma. We investigated inhibition of the GTPase dynamin 2 as a therapy for glioblastoma. Glioma cell lines and patient-derived GSCs were treated with dynamin inhibitors, Dynole 34-2 and CyDyn 4-36. We studied about cell viability, and GSC neurosphere formation in vitro and orthotopic tumour growth in vivo. Dynamin inhibition reduced glioblastoma cell line viability and suppressed neurosphere formation and migration of GSCs. Tumour growth was reduced by CyDyn 4-36 treatment. Dynamin 2 inhibition therefore represents a novel approach for stem cell-directed Glioblastoma therapy.

摘要

胶质瘤干细胞(GSCs)在胶质母细胞瘤的耐药性、肿瘤维持和复发中起主要作用。我们研究了抑制GTP酶发动蛋白2作为胶质母细胞瘤的一种治疗方法。用发动蛋白抑制剂Dynole 34-2和CyDyn 4-36处理胶质瘤细胞系和患者来源的GSCs。我们研究了细胞活力、GSC神经球在体外的形成以及在体内原位肿瘤的生长情况。发动蛋白抑制降低了胶质母细胞瘤细胞系的活力,并抑制了GSCs的神经球形成和迁移。CyDyn 4-36处理使肿瘤生长减缓。因此,抑制发动蛋白2代表了一种针对干细胞的胶质母细胞瘤治疗新方法。

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