Children's Brain Tumour Research Centre, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK.
Nottingham Arabidopsis Stock Centre, Division of Plant and Crop Sciences, School of Biosciences, University of Nottingham, Loughborough LE12 5RD, UK.
Int J Mol Sci. 2022 Feb 11;23(4):1982. doi: 10.3390/ijms23041982.
The lack of treatment options for high-grade brain tumors has led to searches for alternative therapeutic modalities. Electrical field therapy is one such area. The Optune™ system is an FDA-approved novel device that delivers continuous alternating electric fields (tumor treating fields-TTFields) to the patient for the treatment of primary and recurrent Glioblastoma multiforme (GBM). Various mechanisms have been proposed to explain the effects of TTFields and other electrical therapies. Here, we present the first study of genome-wide expression of electrotherapy (delivered via TTFields or Deep Brain Stimulation (DBS)) on brain tumor cell lines. The effects of electric fields were assessed through gene expression arrays and combinational effects with chemotherapies. We observed that both DBS and TTFields significantly affected brain tumor cell line viability, with DBS promoting G0-phase accumulation and TTFields promoting G2-phase accumulation. Both treatments may be used to augment the efficacy of chemotherapy in vitro. Genome-wide expression assessment demonstrated significant overlap between the different electrical treatments, suggesting novel interactions with mitochondrial functioning and promoting endoplasmic reticulum stress. We demonstrate the in vitro efficacy of electric fields against adult and pediatric high-grade brain tumors and elucidate potential mechanisms of action for future study.
对于高级别脑肿瘤缺乏治疗选择，这促使人们寻找替代的治疗方法。电场疗法就是其中之一。Optune™系统是一种获得 FDA 批准的新型设备，可向患者提供连续的交变电场（肿瘤治疗电场-TTFields），用于治疗原发性和复发性多形性胶质母细胞瘤（GBM）。已经提出了各种机制来解释 TTFields 和其他电疗的作用。在这里，我们首次研究了电疗（通过 TTFields 或深部脑刺激（DBS）传递）对脑肿瘤细胞系的全基因组表达的影响。通过基因表达谱和与化疗的组合作用评估电场的影响。我们观察到 DBS 和 TTFields 都显著影响脑肿瘤细胞系的活力，DBS 促进 G0 期积累，TTFields 促进 G2 期积累。这两种治疗方法都可以在体外增强化疗的疗效。全基因组表达评估表明，不同的电疗之间存在显著的重叠，这表明与线粒体功能和促进内质网应激有新的相互作用。我们证明了电场对成人和儿童高级别脑肿瘤的体外疗效，并阐明了未来研究的潜在作用机制。
