STEM-17. IDENTIFICATION OF LOMERIZINE, A PROPHYLACTIC DRUG FOR MIGRAINES, AS A POTENTIAL ANTI-GLIOBLASTOMA DRUG

Abstract

Abstract BACKGROUND Glioblastoma (GBM) is one of the most malignant primary brain tumors. Despite development of treatment, prognosis of GBM is still poor. Here, we identified lomerizine, a prophylactic drug for migraine, as a potential anti-GBM drug from thousands of existing compounds. We investigated its therapeutic effects both in vitro and in vivo with the purpose of drug repositioning. Materials and method: Human patient-derived glioma stem cell line (KGS01, KGS10, KGS15), their differentiated cells, and GBM cell lines (A172, SNB19, T98, U87) were used. Proliferation assay, migration assay, invasion assay and sphere-forming assay were performed. We analyzed various signaling pathways altered by lomerizine by Western blotting. In addition, induction of apoptosis was evaluated by immunofluorescence and Annexin V assay. Anti-GBM effects of lomerizine in vivo with a mouse brain tumor model was validated Result: Lomerizine inhibited proliferation, migration, and invasion dose-dependently in all cell lines, especially in GSCs. Sphere formation was inhibited by lomerizine in all GSCs. STAT3, which is involved in tumorigenesis, was dephosphorylated after the treatment with lomerizine in a dose-dependent manner in all cell lines. Furthermore, lomerizine induced apoptosis in both immunofluorescence and Annexin V assay. In vivo experiments showed a significant tumor suppression and prolongation of overall survival in the group of mice treated with lomerizine. CONCLUSION Lomerizine has anti-GBM effects.