Department of Neurological Surgery, Kagawa University Faculty of Medicine, 1750-1 Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
Department of Pharmacology, Kagawa University Faculty of Medicine, Kagawa, Japan.
Sci Rep. 2023 Jan 16;13(1):808. doi: 10.1038/s41598-023-28133-x.
Glioblastoma is characterized by a strong self-renewal potential and poor differentiated state. We have reported previously that the (pro)renin receptor [(P)RR] is a potential target for glioma therapy by silencing the (P)RR gene. Here, we have examined the effects of a monoclonal antibody against (P)RR on gliomagenesis. Human glioma cell lines (U251MG and U87MG) and a glioma stem cell line (MGG23) were used for the in vitro study. The expressions of the Wnt/β-catenin signaling pathway (Wnt signaling pathway) components and stemness markers were measured by Western blotting. The effects of the (P)RR antibody on cell proliferation, sphere formation, apoptosis and migration were also examined. Subcutaneous xenografts were also examined in nude mice. Treatment with the (P)RR antibody reduced expression of Wnt signaling pathway components and stemness markers. Furthermore, the (P)RR antibody reduced cell proliferation and decreased sphere formation significantly. The treatment also suppressed migration and induced apoptosis. In a subcutaneous xenograft model, systemic administration of the (P)RR antibody reduced tumor volume significantly. These data show that treatment with the (P)RR antibody is a potential therapeutic strategy for treating glioblastoma.
胶质母细胞瘤的特征是具有强大的自我更新能力和低分化状态。我们之前曾报道过,(前)肾素受体[(P)RR]通过沉默(P)RR 基因是一种潜在的治疗神经胶质瘤的靶点。在这里,我们研究了一种针对(P)RR 的单克隆抗体对神经胶质瘤发生的影响。人神经胶质瘤细胞系(U251MG 和 U87MG)和神经胶质瘤干细胞系(MGG23)用于体外研究。通过 Western blot 测定 Wnt/β-catenin 信号通路(Wnt 信号通路)成分和干性标志物的表达。还检查了(P)RR 抗体对细胞增殖、球体形成、细胞凋亡和迁移的影响。还在裸鼠中进行了皮下异种移植研究。(P)RR 抗体的治疗降低了 Wnt 信号通路成分和干性标志物的表达。此外,(P)RR 抗体显著降低了细胞增殖并减少了球体形成。该治疗还抑制了迁移并诱导了细胞凋亡。在皮下异种移植模型中,系统给予(P)RR 抗体可显著降低肿瘤体积。这些数据表明,(P)RR 抗体的治疗是治疗胶质母细胞瘤的一种潜在治疗策略。