Open Access

Inhibition of PI3K signalling increases the efficiency of radiotherapy in glioblastoma cells

  • Authors:
    • Sebastian Hasslacher
    • Lukas Schneele
    • Sebastien Stroh
    • Julia Langhans
    • Katharina Zeiler
    • Patricia Kattner
    • Georg Karpel-Massler
    • Markus D. Siegelin
    • Matthias Schneider
    • Shaoxia Zhou
    • Michael Grunert
    • Marc-Eric Halatsch
    • Lisa Nonnenmacher
    • Klaus-Michael Debatin
    • Mike-Andrew Westhoff
  • View Affiliations

  • Published online on: August 16, 2018     https://doi.org/10.3892/ijo.2018.4528
  • Pages: 1881-1896
  • Copyright: © Hasslacher et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glioblastoma, the most common primary brain tumour, is also considered one of the most lethal cancers per se. It is highly refractory to therapeutic intervention, as highlighted by the mean patient survival of only 15 months, despite an aggressive treatment approach, consisting of maximal safe surgical resection, followed by radio- and chemotherapy. Radiotherapy, in particular, can have effects on the surviving fractions of tumour cells, which are considered adverse to the desired clinical outcome: It can induce increased cellular proliferation, as well as enhanced invasion. In this study, we established that differentiated glioblastoma cells alter their DNA repair response following repeated exposure to radiation and, therefore, high single-dose irradiation (SD-IR) is not a good surrogate marker for fractionated dose irradiation (FD-IR), as used in clinical practice. Integrating irradiation into a combination therapy approach, we then investigated whether the pharmacological inhibition of PI3K signalling, the most abundantly activated survival cascade in glioblastoma, enhances the efficacy of radiotherapy. Of note, treatment with GDC-0941, which blocks PI3K-mediated signalling, did not enhance cell death upon irradiation, but both treatment modalities functioned synergistically to reduce the total cell number. Furthermore, GDC-0941 not only prevented the radiation-induced increase in the motility of the differentiated cells, but further reduced their speed below that of untreated cells. Therefore, combining radiotherapy with the pharmacological inhibition of PI3K signalling is a potentially promising approach for the treatment of glioblastoma, as it can reduce the unwanted effects on the surviving fraction of tumour cells.
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November-2018
Volume 53 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Hasslacher S, Schneele L, Stroh S, Langhans J, Zeiler K, Kattner P, Karpel-Massler G, Siegelin MD, Schneider M, Zhou S, Zhou S, et al: Inhibition of PI3K signalling increases the efficiency of radiotherapy in glioblastoma cells. Int J Oncol 53: 1881-1896, 2018
APA
Hasslacher, S., Schneele, L., Stroh, S., Langhans, J., Zeiler, K., Kattner, P. ... Westhoff, M. (2018). Inhibition of PI3K signalling increases the efficiency of radiotherapy in glioblastoma cells. International Journal of Oncology, 53, 1881-1896. https://doi.org/10.3892/ijo.2018.4528
MLA
Hasslacher, S., Schneele, L., Stroh, S., Langhans, J., Zeiler, K., Kattner, P., Karpel-Massler, G., Siegelin, M. D., Schneider, M., Zhou, S., Grunert, M., Halatsch, M., Nonnenmacher, L., Debatin, K., Westhoff, M."Inhibition of PI3K signalling increases the efficiency of radiotherapy in glioblastoma cells". International Journal of Oncology 53.5 (2018): 1881-1896.
Chicago
Hasslacher, S., Schneele, L., Stroh, S., Langhans, J., Zeiler, K., Kattner, P., Karpel-Massler, G., Siegelin, M. D., Schneider, M., Zhou, S., Grunert, M., Halatsch, M., Nonnenmacher, L., Debatin, K., Westhoff, M."Inhibition of PI3K signalling increases the efficiency of radiotherapy in glioblastoma cells". International Journal of Oncology 53, no. 5 (2018): 1881-1896. https://doi.org/10.3892/ijo.2018.4528