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BioMed Research International
Volume 2014, Article ID 453497, 9 pages
http://dx.doi.org/10.1155/2014/453497
Research Article

Effects of Single or Combined Treatments with Radiation and Chemotherapy on Survival and Danger Signals Expression in Glioblastoma Cell Lines

1Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy
2Department of Medical Physics, IRCCS Policlinico S. Matteo Foundation, Viale Golgi 19, 27100 Pavia, Italy
3Department of Earth and Environmental Sciences, University of Pavia, Via Ferrata 1, 27100 Pavia, Italy

Received 5 April 2014; Accepted 10 June 2014; Published 1 July 2014

Academic Editor: Zhen Chen

Copyright © 2014 Francesca Pasi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The success of chemo- and radiotherapy in glioblastoma multiforme, the most common and lethal primary brain tumour, could rely on the induction of immunogenic tumour cell death and on the induction of anticancer immune response. In this study we investigated cell survival to single treatments or combination of X-rays and temozolomide in glioblastoma cell lines (T98G and U251MG) and we attempted to identify danger signals (HMGB1 and HSP70) released by dying cells in the microenvironment that could activate antitumour immunity contributing to the therapeutic efficacy of conventional treatments. Our data suggest that HSP70 translocates from cytoplasm to extracellular environment after an increase in radiation dose and HMGB1 translocates from the nucleus to the cytoplasm and subsequently is released into the extracellular space, confirming a role of these proteins as signals released after radiation-induced damage in glioblastoma cells. We also could state that TMZ had limited effectiveness in activating HMGB1 and HSP70 signalling and, instead, an adjuvant effect was observed in some combined treatments, depending on schedule, cell line, and timing. A big challenge in tumour therapy is, therefore, to identify the most beneficial combination and chronology of multiple treatment options to contribute to the improvement of the therapeutic outcome.