Cytotoxic and radiosensitizing effects of FAK targeting in human glioblastoma cells in vitro

Research output: Contribution to journalResearch articleContributedpeer-review



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.


Original languageEnglish
Pages (from-to)2009-16
Number of pages8
JournalOncology reports
Issue number4
Publication statusPublished - Apr 2015

External IDs

researchoutputwizard legacy.publication#67938
PubMed 25625667
Scopus 84924912272
ORCID /0000-0001-5684-629X/work/147143563


Sustainable Development Goals


  • Apoptosis/drug effects, Autophagy/drug effects, Cell Line, Tumor, Cell Survival/drug effects, Focal Adhesion Kinase 1/metabolism, Glioblastoma/drug therapy, Humans, Morpholines/pharmacology, Phosphorylation/drug effects, Radiation Tolerance/drug effects, Radiation-Sensitizing Agents/pharmacology, Signal Transduction/drug effects