The Effect of the Combination of Temozolomide and Flubendazole on Glioblastoma Cells.

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by rapid development of chemoresistance and poor patient survival. Due to the limited efficacy of current therapeutic protocols, alternative approaches are needed. One potential strategy is combined treatment with DNA-damaging and microtubule-targeting agents. This study investigated the biological effects of temozolomide (TMZ) and flubendazole (FLU) co-treatment in cultured GBM cells. Three GBM cell lines (A172, T98G, and U118MG) with different molecular profiles were treated with TMZ, FLU, or their combination. Treatment effects were evaluated using WST-1 assay, microscopy, flow cytometry, RT-PCR, and Western blotting. Drug accumulation in tumor and brain tissues was additionally analyzed in a nu-nu mouse model using LC/MS. Combined TMZ and FLU treatment reduced cell proliferation compared with untreated control and TMZ monotherapy in the tested GBM cell lines. FLU-containing treatments were associated with morphological alterations, caspase activation, altered microtubule organization, and G2/M cell cycle accumulation. In addition, co-administration of TMZ and FLU affected drug accumulation in vitro and in brain and tumor tissues in vivo. These findings suggest that the microtubule targeting may modulate the response of GBM cells to TMZ. However, the pharmacological interaction and potential relevance of TMZ + FLU co-treatment require further preclinical validation.