Abstract : Glioblastoma (GBM) is one of the most lethal types of tumor due to its high recurrence level in spite of aggressive treatment regimens involving surgery, radiotherapy and chemotherapy. Hypoxia is a feature of GBM, involved in radioresistance, and is known to be at the origin of treatment failure. The aim of this work was to assess the therapeutic potential of a new targeted c-SRC inhibitor molecule, named Si306, in combination with X-rays on the human glioblastoma cell lines, comparing normoxia and hypoxia conditions. For this purpose, the dose modifying factor and oxygen enhancement ratio were calculated to evaluate the Si306 radiosensitizing effect. DNA damage and the repair capability were also studied from the kinetic of γ-H2AX immunodetection. Furthermore, motility processes being supposed to be triggered by hypoxia and irradiation, the role of c-SRC inhibition was also analyzed to evaluate the migration blockage by wound healing assay. Our results showed that inhibition of the c-SRC protein enhances the radiotherapy efficacy both in normoxic and hypoxic conditions. These data open new opportunities for GBM treatment combining radiotherapy with molecularly targeted drugs to overcome radioresistance.
https://hal-normandie-univ.archives-ouvertes.fr/hal-02861596 Contributor : Carole BrunaudConnect in order to contact the contributor Submitted on : Thursday, December 10, 2020 - 9:05:23 AM Last modification on : Wednesday, May 25, 2022 - 5:28:14 PM Long-term archiving on: : Thursday, March 11, 2021 - 6:41:37 PM
Filippo Torrisi, Luigi Minafra, Francesco Cammarata, Gaetano Savoca, Marco Calvaruso, et al.. SRC Tyrosine Kinase Inhibitor and X-rays Combined Effect on Glioblastoma Cell Lines. International Journal of Molecular Sciences, MDPI, 2020, 21 (11), pp.3917. ⟨10.3390/ijms21113917⟩. ⟨hal-02861596⟩