Eribulin prolongs survival in an orthotopic xenograft mouse model of malignant meningioma

Cancer Sci. 2022 Feb;113(2):697-708. doi: 10.1111/cas.15221. Epub 2021 Dec 8.

Abstract

Meningioma is the most common intracranial tumor, with generally favorable patient prognosis. However, patients with malignant meningioma typically experience recurrence, undergo multiple surgical resections, and ultimately have a poor prognosis. Thus far, effective chemotherapy for malignant meningiomas has not been established. We recently reported the efficacy of eribulin (Halaven) for glioblastoma with a telomerase reverse transcriptase (TERT) promoter mutation. This study investigated the anti-tumor effect of eribulin against TERT promoter mutation-harboring human malignant meningioma cell lines in vitro and in vivo. Two meningioma cell lines, IOMM-Lee and HKBMM, were used in this study. The strong inhibition of cell proliferation by eribulin via cell cycle arrest was demonstrated through viability assay and flow cytometry. Apoptotic cell death in malignant meningioma cell lines was determined through vital dye assay and immunoblotting. Moreover, a wound healing assay revealed the suppression of tumor cell migration after eribulin exposure. Intraperitoneal administration of eribulin significantly prolonged the survival of orthotopic xenograft mouse models of both malignant meningioma cell lines implanted in the subdural space (P < .0001). Immunohistochemistry confirmed apoptosis in brain tumor tissue treated with eribulin. Overall, these results suggest that eribulin is a potential therapeutic agent for malignant meningiomas.

Keywords: TERT promoter mutation; apoptosis; eribulin; malignant meningioma; microtubule inhibitor.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Furans / pharmacology
  • Furans / therapeutic use*
  • Humans
  • Kaplan-Meier Estimate
  • Ketones / pharmacology
  • Ketones / therapeutic use*
  • Meningeal Neoplasms / drug therapy*
  • Meningeal Neoplasms / genetics
  • Meningeal Neoplasms / mortality
  • Meningeal Neoplasms / pathology
  • Meningioma / drug therapy*
  • Meningioma / genetics
  • Meningioma / mortality
  • Meningioma / pathology
  • Mice
  • Mutation
  • Promoter Regions, Genetic
  • Telomerase / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Furans
  • Ketones
  • TERT protein, human
  • Telomerase
  • eribulin