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Published on: March 28, 2021
The Effect of the Combination of Temozolomide and Flubendazole on Glioblastoma Cells
Katerina Kapickova1, Barbora Vitovcova2, Veronika Skarkova1
1Department of Medical Biology and Genetics, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, 500 03 Hradec Kralove, Czech Republic.
Abstract:
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.
Insights
Combining temozolomide (TMZ) and flubendazole (FLU) shows promise for glioblastoma treatment by reducing cell proliferation. This combination therapy impacts cell cycle and drug accumulation, warranting further investigation.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor outcomes due to chemoresistance.
- Current therapies for GBM have limited efficacy, necessitating novel treatment strategies.
- Combined treatment with DNA-damaging and microtubule-targeting agents is a potential therapeutic approach.
Purpose of the Study:
- To investigate the biological effects of co-administering temozolomide (TMZ) and flubendazole (FLU) in glioblastoma cells.
- To evaluate the impact of this combination on cell proliferation, cell cycle, and drug accumulation.
Main Methods:
- Utilized three glioblastoma cell lines (A172, T98G, U118MG) for in vitro studies.
- Assessed treatment effects using WST-1 assay, microscopy, flow cytometry, RT-PCR, and Western blotting.
- Analyzed drug accumulation in vivo using LC/MS in a mouse model.
Main Results:
- Combined TMZ and FLU treatment significantly reduced glioblastoma cell proliferation compared to monotherapy.
- Flubendazole-containing treatments induced morphological changes, caspase activation, and G2/M cell cycle arrest.
- Co-administration of TMZ and FLU influenced drug accumulation in vitro and in vivo brain/tumor tissues.
Conclusions:
- Microtubule targeting by flubendazole may modulate glioblastoma cell response to temozolomide.
- The combination of TMZ and FLU demonstrates potential for glioblastoma treatment.
- Further preclinical validation is required to confirm the pharmacological interaction and clinical relevance.
