Proton therapy and src family kinase inhibitor combined treatments on U87 human glioblastoma multiforme cell line

Francesco P. Cammarata, Filippo Torrisi, Giusi I. Forte, Luigi Minafra*, Valentina Bravatà, Pietro Pisciotta, Gaetano Savoca, Marco Calvaruso, Giada Petringa, Giuseppe A.P. Cirrone, Anna L. Fallacara, Laura Maccari, Maurizio Botta, Silvia Schenone, Rosalba Parenti, Giacomo Cuttone, Giorgio Russo

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

31 Citaten (Scopus)
12 Downloads (Pure)

Samenvatting

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.

Originele taal-2English
Artikelnummer4745
Aantal pagina's18
TijdschriftInternational Journal of Molecular Sciences
Volume20
Nummer van het tijdschrift19
DOI's
StatusPublished - 1-okt.-2019
Extern gepubliceerdJa

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