gms | German Medical Science

Objective: Hyperthermia can induce cell death in human glioblastoma cell lines. In vivo hyperthermia will affect glioblastoma cells and normal human astrocytes. The aim of this study was to evaluate the effect of hyperthermia on calcium metabolism, apoptosis, and necrosis in the human glioblastoma cell line (G28) compared to normal human astrocytes.

Method: Cultured glioblastoma cells (G28) were loaded with the fluorescence calcium indicator FURA-2. Hyperthermia was applied for 1 hour at different temperatures (38°-45°). Intracellular calcium metabolism was evaluated during hyperthermia. Apoptosis and necrosis were determined 1h and 24h after onset of hyperthermia by staining with Hoechst33342 and propidium iodide.

Results: In human glioblastoma cells (G28) a rise in temperature from 37°C to 44°C lead to a significant increase of intracellular calcium metabolism accompanied by a significant increase of necrosis from 4.62% ± 3.16% at 38° to 32.23% ± 2.53% at 44° (p<0.001). In human astrocytes hyperthermia from 38°C to 44°C lead to a rise of intracellular calcium concentration and a significant increase of necrosis from 5.62% ± 2.23% at 38° to 36.27% ± 20.07% at 44° (p<0.001). Apoptosis rates increased by higher temperature in G28 cells from 5.95% ± 1.16% at 38° to 9.47% ± 1.77% (p<0.001) at 44° and from 4.70% ± 1.44% at 38° to 12.45% ± 4.28% at 44° in human astrocytes (p<0.001). Hyperthermia of 45°C induced massive necrosis of 67.27% ± 25.34% in G28 cells but only moderate necrosis of 34.77% ± 11.10% in human astrocytes.

Conclusions: This study suggests that hyperthermia in the treatment of GBM induces cell death in human glioblastoma cell lines and in human astrocytes with temperatures ≥44°. Human astrocytes are more resistant to temperatures up to 45° than G28 cells. In G28 cells temperatures ≥45° are needed for sufficient cell death rates after hyperthermia.