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Article

Proton Therapy and Src Family Kinase Inhibitor Combined Treatments on U87 Human Glioblastoma Multiforme Cell Line

by
Francesco P Cammarata
1,2,†,
Filippo Torrisi
2,3,†,
Giusi I Forte
1,2,
Luigi Minafra
1,2,*,
Valentina Bravatà
1,2,
Pietro Pisciotta
2,4,
Gaetano Savoca
1,
Marco Calvaruso
1,2,
Giada Petringa
2,3,
Giuseppe A. P. Cirrone
2,
Anna L Fallacara
5,6,
Laura Maccari
5,
Maurizio Botta
5,6,
Silvia Schenone
7,
Rosalba Parenti
3,
Giacomo Cuttone
2 and
Giorgio Russo
1,2
1
Institute of Molecular Bioimaging and Physiology, National Research Council, IBFM-CNR, 90015 Cefalù, Italy
2
National Institute for Nuclear Physics, Laboratori Nazionali del Sud, INFN-LNS, 95123 Catania, Italy
3
Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, 95123 Catania, Italy
4
Departments of Physics and Astronomy, University of Catania, 95123 Catania, Italy
5
Lead Discovery Siena s.r.l. (LDS), 53100 Siena, Italy
6
Department of Biotechnology, Chemistry and Pharmacy, Università degli Studi di Siena, 53100 Siena, Italy
7
Department of Pharmacy, Università degli Studi di Genova, 16126 Genova, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(19), 4745; https://doi.org/10.3390/ijms20194745
Submission received: 3 September 2019 / Revised: 17 September 2019 / Accepted: 24 September 2019 / Published: 24 September 2019
(This article belongs to the Special Issue Radiation Damage in Biomolecules and Cells)
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Abstract

Glioblastoma Multiforme (GBM) is the most common of malignant gliomas in adults with an exiguous life expectancy. Standard treatments are not curative and the resistance to both chemotherapy and conventional radiotherapy (RT) plans is the main cause of GBM care failures. Proton therapy (PT) shows a ballistic precision and a higher dose conformity than conventional RT. In this study we investigated the radiosensitive effects of a new targeted compound, SRC inhibitor, named Si306, in combination with PT on the U87 glioblastoma cell line. Clonogenic survival assay, dose modifying factor calculation and linear-quadratic model were performed to evaluate radiosensitizing effects mediated by combination of the Si306 with PT. Gene expression profiling by microarray was also conducted after PT treatments alone or combined, to identify gene signatures as biomarkers of response to treatments. Our results indicate that the Si306 compound exhibits a radiosensitizing action on the U87 cells causing a synergic cytotoxic effect with PT. In addition, microarray data confirm the SRC role as the main Si306 target and highlights new genes modulated by the combined action of Si306 and PT. We suggest, the Si306 as a new candidate to treat GBM in combination with PT, overcoming resistance to conventional treatments.
Keywords: glioblastoma multiforme; proton therapy; combined treatments; gene signatures glioblastoma multiforme; proton therapy; combined treatments; gene signatures

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MDPI and ACS Style

Cammarata, F.P.; Torrisi, F.; Forte, G.I.; Minafra, L.; Bravatà, V.; Pisciotta, P.; Savoca, G.; Calvaruso, M.; Petringa, G.; Cirrone, G.A.P.; et al. Proton Therapy and Src Family Kinase Inhibitor Combined Treatments on U87 Human Glioblastoma Multiforme Cell Line. Int. J. Mol. Sci. 2019, 20, 4745. https://doi.org/10.3390/ijms20194745

AMA Style

Cammarata FP, Torrisi F, Forte GI, Minafra L, Bravatà V, Pisciotta P, Savoca G, Calvaruso M, Petringa G, Cirrone GAP, et al. Proton Therapy and Src Family Kinase Inhibitor Combined Treatments on U87 Human Glioblastoma Multiforme Cell Line. International Journal of Molecular Sciences. 2019; 20(19):4745. https://doi.org/10.3390/ijms20194745

Chicago/Turabian Style

Cammarata, Francesco P, Filippo Torrisi, Giusi I Forte, Luigi Minafra, Valentina Bravatà, Pietro Pisciotta, Gaetano Savoca, Marco Calvaruso, Giada Petringa, Giuseppe A. P. Cirrone, and et al. 2019. "Proton Therapy and Src Family Kinase Inhibitor Combined Treatments on U87 Human Glioblastoma Multiforme Cell Line" International Journal of Molecular Sciences 20, no. 19: 4745. https://doi.org/10.3390/ijms20194745

APA Style

Cammarata, F. P., Torrisi, F., Forte, G. I., Minafra, L., Bravatà, V., Pisciotta, P., Savoca, G., Calvaruso, M., Petringa, G., Cirrone, G. A. P., Fallacara, A. L., Maccari, L., Botta, M., Schenone, S., Parenti, R., Cuttone, G., & Russo, G. (2019). Proton Therapy and Src Family Kinase Inhibitor Combined Treatments on U87 Human Glioblastoma Multiforme Cell Line. International Journal of Molecular Sciences, 20(19), 4745. https://doi.org/10.3390/ijms20194745

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