Ahlstedt Jonatan, Förnvik Karolina, Zolfaghari Shaian, Kwak Dongoh, Hammarström Lars G J, Ernfors Patrik, Salford Leif G, Redebrandt Henrietta Nittby
Rausing Laboratory, Division of Neurosurgery, Department of Clinical Sciences Lund, Lund University, Lund, Sweden, Lund University, Sweden.
Department of Medical Biochemistry and Biophysics, Division of Molecular Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Oncotarget. 2018 Jan 3;9(9):8391-8399. doi: 10.18632/oncotarget.23842. eCollection 2018 Feb 2.
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, and available experimental and routine therapies result in limited survival benefits. A vulnerability of GBM cells to catastrophic vacuolization and cell death, a process termed methuosis, induced by Vacquinol-1 (VQ-1) has been described earlier. In the present study, we investigate the efficacy of VQ-1 treatment in two syngeneic rat GBM models, RG2 and NS1. VQ-1 treatment affected growth of both RG2 and NS1 cells . Intracranially, significant reduction in RG2 tumor size was observed, although no effect was seen on overall survival. No survival advantage or effect on tumor size was seen in animals carrying the NS1 models compared to untreated controls. Furthermore, immunological staining of FOXP3, CD4 and CD8 showed no marked difference in immune cell infiltrate in tumor environment following treatment. Taken together, a survival advantage of VQ-1 treatment alone could not be demonstrated here, even though some effect upon tumor size was seen. Staining for immune cell markers did not indicate that VQ-1 either reduced or increased host anti-tumor immune response.
多形性胶质母细胞瘤(GBM)是最常见的原发性恶性脑肿瘤,现有的实验性和常规治疗方法带来的生存获益有限。此前已有研究报道,Vacquinol-1(VQ-1)可诱导GBM细胞发生灾难性空泡化和细胞死亡,即所谓的methuosis。在本研究中,我们调查了VQ-1在两种同基因大鼠GBM模型RG2和NS1中的治疗效果。VQ-1治疗影响了RG2和NS1细胞的生长。在颅内,观察到RG2肿瘤大小显著减小,尽管对总生存期没有影响。与未治疗的对照组相比,携带NS1模型的动物在生存期或肿瘤大小方面未显示出优势。此外,FOXP3、CD4和CD8的免疫染色显示,治疗后肿瘤环境中的免疫细胞浸润没有明显差异。综上所述,尽管VQ-1对肿瘤大小有一定影响,但单独使用VQ-1治疗并不能带来生存获益。免疫细胞标志物染色并未表明VQ-1会降低或增强宿主的抗肿瘤免疫反应。