Morimoto Mari, Toyoda Hidemi, Niwa Kaori, Hanaki Ryo, Okuda Taro, Nakato Daisuke, Amano Keishiro, Iwamoto Shotaro, Hirayama Masahiro
Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
Mol Clin Oncol. 2022 Jul 21;17(3):138. doi: 10.3892/mco.2022.2571. eCollection 2022 Sep.
Neuroblastoma is a highly malignant disease with a poor prognosis and few treatment options. Despite conventional chemotherapy for neuroblastoma, resistance, invasiveness, and metastatic mobility limit the treatment efficacy. Therefore, it is necessary to develop new strategies for treating neuroblastoma. The present study aimed to evaluate the anticancer effects of nafamostat mesylate, a previously known serine protease inhibitor, on neuroblastoma cells. Effects of nafamostat mesylate on neuroblastoma cell migration and proliferation were analyzed by wound healing assay and WST-8 assay, respectively. To elucidate the mechanisms underlying the effects of nafamostat mesylate on neuroblastoma, the expression levels of NF-κB were measured via western blotting, and the production of the cytokine vascular endothelial growth factor (VEGF) in the cell culture supernatants was determined via ELISA. In addition, a mouse model of hematogenous metastasis was used to investigate the effects of nafamostat mesylate on neuroblastoma. It was determined that nafamostat mesylate significantly inhibited migration and invasion of Neuro-2a cells, but it had no effect on cell proliferation at 24 h after treatment. Exposure of Neuro-2a cells to nafamostat mesylate resulted in decreased vascular endothelial growth factor production, which could be a pivotal mechanism underlying the inhibitory effects of neuroblastoma metastasis. The results of the present study suggest that nafamostat mesylate may be an effective treatment against neuroblastoma invasion and metastasis.
神经母细胞瘤是一种高度恶性的疾病，预后较差且治疗选择有限。尽管对神经母细胞瘤采用了传统化疗，但耐药性、侵袭性和转移活性限制了治疗效果。因此，有必要开发治疗神经母细胞瘤的新策略。本研究旨在评估甲磺酸萘莫司他（一种已知的丝氨酸蛋白酶抑制剂）对神经母细胞瘤细胞的抗癌作用。分别通过伤口愈合试验和WST-8试验分析了甲磺酸萘莫司他对神经母细胞瘤细胞迁移和增殖的影响。为了阐明甲磺酸萘莫司他对神经母细胞瘤作用的潜在机制，通过蛋白质印迹法测量NF-κB的表达水平，并通过酶联免疫吸附测定法测定细胞培养上清液中细胞因子血管内皮生长因子（VEGF）的产生。此外，使用血行转移小鼠模型研究甲磺酸萘莫司他对神经母细胞瘤的影响。结果确定，甲磺酸萘莫司他显著抑制Neuro-2a细胞的迁移和侵袭，但在处理后24小时对细胞增殖没有影响。Neuro-2a细胞暴露于甲磺酸萘莫司他导致血管内皮生长因子产生减少，这可能是神经母细胞瘤转移抑制作用的关键机制。本研究结果表明，甲磺酸萘莫司他可能是治疗神经母细胞瘤侵袭和转移的有效药物。
