Nafamostat mesylate prevents metastasis and dissemination of neuroblastoma through vascular endothelial growth factor inhibition

Mari Morimoto, Hidemi Toyoda, Kaori Niwa, Ryo Hanaki, Taro Okuda, Daisuke Nakato, Keishiro Amano, Shotaro Iwamoto, Masahiro Hirayama

Research output: Contribution to journalArticlepeer-review


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 inhib-itor, 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 superna-tants 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.

Original languageEnglish
Article number138
JournalMolecular and Clinical Oncology
Issue number3
Publication statusPublished - 2022 Sept
Externally publishedYes


  • metastasis
  • murine model
  • nafamostat mesylate
  • neuroblastoma
  • vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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