Glioblastoma multiforme (GBM) is a highly aggressive and extremely lethal
cancer and novel molecular
therapies are required for optimized multimodal
therapy regimes. While focal adhesion kinase (FAK) is regarded as a therapeutic target, its radiosensitizing potential remains to be elucidated in
glioblastoma. Thus, FAK was inhibited using the pharmaco-logical inhibitor
TAE226 and cytotoxicity and radiosensitization of
glioblastoma cells were investigated in vitro. Monolayer and
suspension cell cultures of a panel of
glioblastoma cell lines (A172, LN229, U87MG, U138MG, U343MG, DD-HT7607, and DD-T4) were treated with increasing
TAE226 concentrations (0-10 µM) alone or in combination with X-rays (0-6 Gy). Subsequently, clonogenic cell survival, expression and the phosphorylation of FAK downstream signaling, apoptosis and autophagy were analyzed. Efficient FAK inhibition by
TAE226 mediated significant cytotoxicity and reduced sphere formation in a dose- and time-dependent manner. Two out of seven
glioblastoma cell lines showed radiosensitization. Apoptotic induction by
TAE226 was cell line-dependent. The results demonstrated that pharmacological FAK inhibitor
TAE226 efficiently reduced clonogenicity and sphere formation in
glioblastoma cells without generally modifying their radiosensitivity. However, future studies are necessary to define the potential of FAK inhibition by
TAE226 or other pharmacological inhibitors in combination with
radiochemotherapy.