Article
The effect of temozolomide and combined mild hyperthermia on human glioblastoma cell lines
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Authors
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Mahapara Sultan
- Neurchirurgische Klinik, Justus Liebig Universität Giessen, Germany
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Malgorzata Kolodziej
- Neurchirurgische Klinik, Justus Liebig Universität Giessen, Germany
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Marcus Reinges
- Neurchirurgische Klinik, Justus Liebig Universität Giessen, Germany
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Eberhard Uhl
- Neurchirurgische Klinik, Justus Liebig Universität Giessen, Germany
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Marco Stein
- Neurchirurgische Klinik, Justus Liebig Universität Giessen, Germany
| Published: | June 2, 2015 |
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Outline
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Objective: Glioblastoma multiforme (GBM) represents the most common and malignant brain tumor. Current therapies focus on maximum safe resection, chemotherapy and radiotherapy. Nevertheless, overall survival remains limited in these patients. Recent studies support the hypothesis, that mild additional hyperthermia could improve the effect of additional chemo- or radiotherapy. This study was conducted to observe the impact of mild hyperthermia in combination with temozolomide (TMZ) on human glioblastoma cell lines.
Method: For this study the human glioblastoma cell lines A172 and G28 were incubated with 50 μM TMZ for 24 to 72 h. Different groups with mild hyperthermia (40° to 42°) before and after the incubation with TMZ and a control group at 37° were studied. Cell proliferation was measured by extinction index (ETI) with MTT assay at 24, 48, and 72 hours after incubation with TMZ.
Results: Cell proliferation at 42° was highest in A172 cells (ETI: 0.53 ± 0.14) and lowest in G28 cells (ETI: 0.26 ± 0.07). The combination of mild hyperthermia at 42° and TMZ reduced viable A172 and G28 cells at 72 h to 38.94% ± 7.13% and 87.13% ± 8.61%, respectively. Analogous results were obtained for A172 and G28 cells at 40° with mean viable cells of 37.69% ± 12.16% and 87.36% ± 5.83% at 72 h using 50 μM TMZ. In the control group at 37° TMZ did not reduce viable cell counts below 65.67% in A172 cells. Furthermore, a cell proliferation to 113.06% ± 29.54% in G28 cells was observed at 37° after incubation with 50 μM TMZ.
Conclusions: These results suggest that mild hyperthermia could have an additional effect on cell proliferation in combination with TMZ in human glioblastoma cell lines. This effect is most visible in fast growing glioblastoma cell lines.
