LAUSR

Corticosteroids are widely used in the management of glioblastoma, primarily for the control of peritumoral edema. However, their direct impact on tumor cell biology remains poorly defined. In vitro studies are often limited by the use of fetal bovine serum (FBS), which contains variable amounts of steroid hormones that can activate the glucocorticoid receptor (GR), confounding data interpretation. This study aimed to (1) characterize the functional activity of GR in glioblastoma cell lines, and (2) evaluate the effects of increasing concentrations of glucocorticoids on tumor cell viability under clinically relevant conditions, including exposure to temozolomide (TMZ) and ionizing radiation. U87MG and U118MG glioblastoma cell lines were cultured in medium supplemented with steroid-depleted FBS. GR functionality was assessed using a luciferase reporter assay driven by the MMTV promoter, with dexamethasone (DEX, 10 nM) stimulation and RU486 inhibition. For viability assays, cells were treated with DEX (1-1000 nM), with or without TMZ (30 µg/mL), followed by 5 Gy irradiation. Viability was measured over 96 h using CCK-8. Data were analyzed by one-way or two-way ANOVA with Bonferroni correction. Both cell lines exhibited functional GR activity, as evidenced by DEX-induced luciferase expression, which was inhibited by RU486. Despite lower transfection efficiency in U87MG, GR responsiveness was confirmed in both lines. Under basal conditions, DEX increased cell viability in both lines, peaking at 48 h. In U87MG, 10 nM DEX produced the most robust effect (~75% increase), whereas U118MG showed a more moderate but consistent response (~25%), even at the lowest dose. Radiation modulated these effects: in U87MG, DEX retained partial cytoprotection (notably at 1-10 nM), while in U118MG, high doses of DEX (100-1000 nM) exacerbated radiation-induced cytotoxicity. Co-treatment with TMZ revealed a dose-dependent modulation: in U87MG, 10 nM DEX rescued viability while 1 nM DEX worsened the cytotoxic effect. These interactions were nullified by radiotherapy. In contrast, U118MG maintained the protective effect of DEX10 even in the presence of radiation. Dexamethasone exerts a dose- and time-dependent prosurvival effect in glioblastoma cells, modulating their response to both chemotherapy and radiotherapy. The divergent responses observed between cell lines highlight the importance of tumor-specific factors in determining glucocorticoid sensitivity. These findings support a more personalized and cautious use of corticosteroids in glioblastoma treatment protocols, particularly when combined with cytotoxic therapies.