Mebendazole Shows Antiproliferative and Antimigratory Effects in Paediatric Low-Grade Glioma Models

Objectives: Advances in molecular profiling of pediatric low-grade glioma have enabled targeted therapies to emerge as effective and better-tolerated alternatives to conventional chemotherapy, increasingly used in progressive or recurrent disease and may reduce long-term treatment toxicity. This study aimed to evaluate the repositioning of the anthelmintic drug mebendazole (MBZ) as an antiproliferative agent in pediatric glioma models, and to investigate potential synergistic effects in combination with vinblastine. Methods: Two well-established human pediatric glioma cell lines, RES 259 and RES 186, were exposed to MBZ alone or in combination with vinblastine. Cell viability, cytotoxicity, and tumor invasiveness were assessed using functional assays. The effects of MBZ on intracellular signaling pathways, particularly Mitogen-Activated Protein (MAP) kinase and on migration-related proteins, were further analyzed. Results: MBZ treatment for 48 h induced cytotoxicity and significantly inhibited cell growth in both RES 259 and RES 186. In addition, MBZ demonstrated anti-migratory and disrupted MAP kinase signaling. Experiments investigating combination treatment revealed that MBZ and vinblastine did not exert synergistic or additive effects, likely due to their shared targeting of microtubule dynamics. Conclusion: These findings indicate that MBZ exerts potent antiproliferative and anti-migratory activity in pediatric glioma cell lines, supporting its potential as a repositioned therapeutic drug. However, no additional benefit was observed when combined with vinblastine, underscoring the importance of exploring MBZ as a single-agent strategy in future translational studies.