SRC Tyrosine Kinase Inhibitor and X-rays Combined Effect on Glioblastoma Cell Lines

被引：26

作者：

Torrisi, Filippo ^{[1
,2
]}

Minafra, Luigi ^{[2
,3
]}

Cammarata, Francesco P. ^{[2
,3
]}

Savoca, Gaetano ^{[2
,3
]}

Calvaruso, Marco ^{[2
,3
]}

Vicario, Nunzio ^{[1
]}

Maccari, Laura ^{[4
]}

Peres, Elodie A. ^{[5
]}

Ozcelik, Hayriye ^{[5
]}

Bernaudin, Myriam ^{[5
]}

Botta, Lorenzo ^{[4
]}

Russo, Giorgio ^{[2
,3
]}

Parenti, Rosalba ^{[1
]}

Valable, Samuel ^{[5
]}

机构：

[1] Univ Catania, Dept Biomed & Biotechnol Sci BIOMETEC, I-95123 Catania, Italy

[2] Ist Nazl Fis Nucl, Lab Nazl Sud, Natl Inst Nucl Phys, LNS, I-95123 Catania, Italy

[3] CNR, Inst Mol Bioimaging & Physiol, CNR, IBFM, I-90015 Cefalu, Italy

[4] Lead Discovery Siena Srl LDS, Via Vittorio Alfieri,31, I-53019 Siena, Italy

[5] Normandie Univ, GIP Cyceron, ISTCT CERVOxy Grp, UNICAEN,CEA,CNRS, F-14074 Caen, France

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 11期

关键词：

Glioblastoma; ionizing radiation; hypoxia; DNA damage; combined treatments; GLIOMA-CELLS; TUMOR HYPOXIA; IN-VIVO; DASATINIB; TEMOZOLOMIDE; RADIATION; TRIAL; MECHANISMS; EFFICACY; RECEPTOR;

D O I：

10.3390/ijms21113917

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 gamma-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.

引用

页数：16

共 42 条

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