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Abstract

Because of the outstanding importance of the glucocorticoid Dexamethasone (DEX) as supportive therapy in the management of brain tumours, the direct effect of DEX on tumour cell proliferation is of particular interest. Previous in vitro studies led to contradictory results. To characterise more precisely the influence of DEX, we investigated the glioblastoma multiforme (GM) cell lines A172, T98G and 86HG39. Cells were treated with DEX concentrations ranging from 5 x 10(-9) to 5 x 10(-5) M from 24 to 240h under different treatment conditions. Influence of DEX on glioma cell viability was assessed daily for 5 days by MTT-assay: (I) with continuous DEX incubation (acute treatment), (II) in a recultivation period without DEX after 5 days of DEX pre-incubation (pre-treatment), (III) with continuous DEX incubation after 5 days of DEX pre-incubation (combination treatment). DEX acute treatment led to strongly decreased proliferation of A172 cells, whereas T98G and 86HG39 cells remained uninfluenced. In opposite, a time-delayed inhibition of cell proliferation was observed in all three cell lines after DEX pre-treatment. Combination treatment induced a significant increase of the inhibitory effect in A172 and T98G cells. These data show a variable, partial time-dependent inhibitory effect of DEX on the proliferation of GM cells and may open new treatment strategies for malignant brain tumours.

Corticosteroids in brain cancer patients: benefits and pitfalls

“…Data from in vitro experiments suggest a variable, time-dependent inhibitory effect of dexamethasone on the proliferation of glioma cells [62]. Stimulatory effects of dexamethasone on glioma cells lines have also been observed at low cell densities and steroid concentration under experimental conditions [63].…”

Dexamethasone in Glioblastoma Multiforme Therapy: Mechanisms and Controversies

“…Dexamethasone (DEX) represents the drug of choice among the synthetic glucocorticoids (GCs) by virtue of its minimal mineralocorticoid activity, long half-life and high potency (Kostaras et al, 2014). By evaluating the typical features of GBM aggressiveness, several studies have shown positive effects of DEX on GBM cells both in vitro and cancer volume, in vivo (Guerin et al, 1992; Wolff et al, 1997; Kaup et al, 2001; Villeneuve et al, 2008; Piette et al, 2009; Fan et al, 2014) although, the mechanisms accounting for these actions remain unclear. Strikingly, contradictory evidence has been published generating controversies that are still debated.…”

A Dexamethasone-regulated Gene Signature Is Prognostic for Poor Survival in Glioblastoma Patients

“…8 A rat model study generated the proposal that dexamethasone reduces both the expression and the response of vascular endothelial growth factor (VEGF), thus reducing edema. 9 Dexamethasone-mediated induction of apoptosis in human glioblastoma cell lines as well as its antitumor activity in xenografted nude rats have been described, 10 and it has also been suggested that dexamethasone reduces invasiveness of human glioblastoma cells in vitro and blood vessel invasion in vivo through a MAPK phosphatase-1–dependent mechanism.…”