+44 330 818 7254Barbora VÃÂtovcová
Glioblastoma multiforme (GBM) is the most invasive and aggressive form of gliomas. Its current therapy consisting of surgical resection, radiotherapy and chemotherapy with orally administrated temozolomide (TMZ) is often unsuccessful. The aim of this study was to compare the effect of TMZ and repurposed drug flubendazole (FLU) on GBM stabilized cell line (A-172) and primary culture obtained from a patient´s biological sample. The effects of TMZ and FLU on GBM cells was evaluated via measurement of cell proliferation rate (WST-1), changes in cellular morphology (phase contrast) and appearance and subcellular localization of microtubular cytoskeleton (fluorescent microscopy). Expression of select chemoresistance markers was determined by western blotting while intracellular accumulation of tested drugs and their metabolites was measured by LC-MS analysis. Our results show that both cellular models differed in their sensitivities to the respective drugs; in both tested cell lines FLU was generally more effective. FLU inhibited proliferation of tested cell, induced formation of multinucleated cells, caused significant changes in microtubules and stimulated cell death. Conversely, TMZ had comparatively lowed antiproliferative effect and did not induce observable cell death. Moreover, its efficiency seemingly corresponded with the expression levels of MRP1 resistance marker (in particular in GBM primary cells) and TMZ intracellular accumulation and metabolism.
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