Glucose Influences the Response of Glioblastoma Cells to Temozolomide and Dexamethasone

Abstract

Objective Current research indicates that weakness of glucose metabolism plays an important role in silencing of invasiveness and growth of hypoxic tumors such as GBM. Moreover, there are indications that DXM, frequently used in treatment, may support GBM energy metabolism and provoke its recurrence. Methods We carried out in vitro experiments on the commercial T98G cell line and two primary GBM lines (HROG02, HROG17) treated with TMZ and/or DXM in physiological oxygen conditions for GBM (2.5% oxygen) and for comparison, in standard laboratory conditions (20% oxygen). The influence of different glucose levels on selected malignancy features of GBM cells-cellular viability and division, dynamic of cell culture changes, colony formation and concentration of InsR have been elevated. Results Under 2.5% oxygen and high glucose concentration, an attenuated cytotoxic effect of TMZ and intensification of malignancy features in all glioblastoma cell lines exposed to DXM was seen. Furthermore, preliminary retrospective analysis to assess the correlation between serum glucose levels and Ki-67 expression in surgical specimens derived from patients with GBM (IV) treated with radio-chemotherapy and prophylactic DXM therapy was performed. Conclusion The data suggest a link between the in vitro study results and clinical data. High glucose can influence on GBM progression through the promotion of the following parameters: cell viability, dispersal, InsR expression and cell proliferation (Ki-67). However, this problem needs more studies and explain the mechanism of action studied drugs.

Characteristics of Blood Levels of Vascular Endothelial Growth Factor A (VEGFA) and Its Receptors in Men with Malignant Brain Gliomas with Different Responses to Combination Therapy

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Unveiling the role of metabolic rates variation in driving tumor heterogeneity and controlling growth and invasion: insights from an integrated multiscale in-vitro in-silico framework

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Cancer- related protein profile of patient-derived and commercial glioblastoma cell lines exposed to Temozolomide

“…For performing protein pro le assay, three lines were cultured according to the previously described method [13]. When the con uency reached about 97%, TMZ was added (or not added in control group) to the culture for 24 hrs and GBM lines were incubated in hypoxia conditions (2.5% oxygen).…”

“…Since our previous study performed on commercial T98G and primary (HROG02, HROG17) human GBM cell lines showed differences in sensitivity of cells to TMZ, induced by changes of glucose and oxygen concentration in culture medium [13], we decided to investigate if and which differences in proteome pro le of analyzed GBM lines could be correlated with this effect. We compared TMZ effects on protein expression in commercial T98G cell line, a GBM lines derived from a patient not treated after resection (HROG02) and a patient with recurrence (HROG17), looking for common or characteristic markers speci c for these lines.…”