Abstract B244: The small molecule focal adhesion kinase inhibitor Y15 decreases human glioblastoma cell viability, clonogenicity, and tumor growth.

Introduction: Glioblastomas are the third most frequent cause of cancer-associated deaths due to the cancer cell rapid growth and high invasion and novel therapeutic approaches are needed for this disease. Focal adhesion Kinase (FAK) is known to be highly expressed and activated in glioblastoma and plays significant role in tumorigenesis. Experimental procedures: In this report we tested FAK autophosphorylation inhibitor, Y15 (called also Inhibitor 14) or 1,2,4,5-Benzenetetraamine tetrahydrochloride) that specifically decreased Y397-FAK autophosphorylation in DBTRG and U87 glioblastoma cells. To test Y15 we used the following in vitro assays: viability, clonogenicity, detachment, apoptosis, invasion, immunostaining, Western blotting and microarray analysis of gene expression; and in vivo assay: xenograft tumor growth model. Results: Y15 significantly decreased viability and clonogenicity of DBTRG and U87 cells in a dose-dependent manner. Y15 inhibitor increased detachment, apoptosis and inhibited cell invasion in a dose-dependent manner. In addition, Y15 decreased autophosphorylation of FAK in a dose-dependent manner and changed cell morphology by causing cell rounding in DBTRG and U87 cells. Moreover, we tested the effect of Y15 on gene expression by Illumina Human HT12v4 microarray assay and among 34, 694 genes affected by Y15 there we 8087 and 6555 genes either up- or down-regulated in DBTRG and U87 cells, respectively (p Conclusion: Inhibition of FAK autophosphorylation with the oral small molecule inhibitor Y15 can be an effective therapy approach to block glioblastoma tumor growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B244.