Ishikawa Takaaki, Matsuda Masahide, Kaneda Yasufumi, Ishikawa Eiichi
Graduate School of Comprehensive Human Sciences, Doctoral Program in Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Department of Neurosurgery, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
J Neurooncol. 2025 Jul 21. doi: 10.1007/s11060-025-05172-0.
Malignant meningiomas are characterized by high recurrence rates and limited therapeutic options beyond surgery and radiation. This study aimed to develop a novel nucleic acid-based therapeutic approach for malignant meningiomas and to evaluate its efficacy both in vitro and in vivo.
IOMM-Lee and HKBMM cell lines were used as models of malignant meningioma. Inhibitory effects of hemagglutinating virus of Japan envelope (HVJ-E) and microRNA-34a-5p (miR-34a-5p) were assessed using cell viability assays, apoptosis assays, RT-qPCR, and western blotting. Finally, the tumor suppressive effect of HVJ-E encapsulating miR-34a-5p was evaluated using a subcutaneous xenograft model in nude mice.
HVJ-E significantly reduced viability of malignant meningioma cells. Furthermore, HVJ-E encapsulating miR-34a-5p demonstrated enhanced anti-tumor activity by inducing apoptosis through downregulation of survivin expression. This tumor-suppressive effect was also confirmed in a subcutaneous mouse model.
Our findings indicate that HVJ-E encapsulating miR-34a-5p effectively inhibits the growth of malignant meningioma cells both in vitro and in vivo. This novel combination therapy holds promise as a potential treatment strategy for malignant meningiomas.
恶性脑膜瘤的特点是复发率高，且除手术和放疗外治疗选择有限。本研究旨在开发一种针对恶性脑膜瘤的新型核酸治疗方法，并在体外和体内评估其疗效。
使用IOMM-Lee和HKBMM细胞系作为恶性脑膜瘤模型。通过细胞活力测定、凋亡测定、RT-qPCR和蛋白质印迹法评估日本血凝病毒包膜（HVJ-E）和微小RNA-34a-5p（miR-34a-5p）的抑制作用。最后，使用裸鼠皮下异种移植模型评估封装miR-34a-5p的HVJ-E的肿瘤抑制作用。
HVJ-E显著降低恶性脑膜瘤细胞的活力。此外，封装miR-34a-5p的HVJ-E通过下调生存素表达诱导凋亡，表现出增强的抗肿瘤活性。这种肿瘤抑制作用在皮下小鼠模型中也得到了证实。
我们的研究结果表明，封装miR-34a-5p的HVJ-E在体外和体内均能有效抑制恶性脑膜瘤细胞的生长。这种新型联合疗法有望成为恶性脑膜瘤的潜在治疗策略。
