Glioblastoma is a brain tumor with a poor survival prognosis. Glioblastoma stem cells (GSC) with their ability to differentiate and providing heterogeneity play an important role in resistance to therapy. The maintenance of these properties is related to their interactions with the tumor microenvironment (TMO). As part of the study, we wanted to understand the difference in the metabolic activity of GSC and differentiated glioblastoma cells (dGB) themselves and in the medium with metabolites of endothelial cells, which is part of the TMO, before and after therapy with temozolomide (TMZ). In this study, we compared the change in cellular metabolic viability and the ultrastructural characteristics of mitochondria using a cell viability test, based on metabolic viability, and transmission electron microscopy. We found that the ultrastructure of mitochondria in dGB and GSC and thus likely also their metabolism differs. Treatment of glioblastoma cells with TMZ cause changes in cell viability and mitochondrial ultrastructure which indicate a decrease in oxidative phosphorylation (OXPHOS) level in dGB, and an increase in OXPHOS activity in GSC. Addition of the endothelial part of the TMO cause changes in cell viability and mitochondrial ultrastructure which indicate that the activity of OXPHOS is reduced in dGB and GSC. With the joint action of TMO and TMZ, changes in cell viability and mitochondrial ultrastructure also point to decreased OXPHOS state in dGB. On the other hand, TMZ has no effect on the GSC with the addition of TMO. We found that the response of GSC can indicate their resistance to therapy, which plays a major role in tumor recurrence. Since not much is known about the metabolic state of dGB and GSC, our data significantly contribute to a better understanding of glioblastoma gained resistance upon therapy.
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