Focal adhesion is known to be highly expressed and activated in
glioma cells. Recently, we demonstrated that FAK autophosphorylation inhibitor, Y15 significantly decreased
tumor growth of DBTRG and U87 cells, especially in combination with
temozolomide. In the present report, we performed gene expression analysis in these cells to reveal genes affected by Y15,
temozolomide and combination of Y15 and
temozolomide. We tested the effect of Y15 on gene expression by Illumina Human HT12v4 microarray assay and detected 8087 and 6555 genes, which were significantly either up- or down-regulated by Y15-treatment in DBTRG and U87 cells, respectively (p<0.05). Moreover, DBTRG and U87 cells treated with Y15 changed expression of 1332 and 462 genes more than 1.5 fold, p<0.05, respectively and had 237 common genes affected by Y15. The common genes up-regulated by Y15 included GADD45A, HSPA6 (heat-shock 70); DUSP1, DUSP 5 (dual-
phosphatase 5); CDKN1A (p21) and common down-regulated genes included
kinesins, such as KIF11, 14, 20A, 20B;
topoisomerase II, TOP2A;
cyclin F; cell cycle
protein: BUB1; PARP1, POLA1. In addition, we detected genes affected by
temozolomide and by combination of Y15 and
temozolomide treatment in U87 cells. Among genes up-regulated by Y15 and
temozolomide more significantly than by each agent alone were: COX7B;
interferon, gamma-inducible transcript: IFI16; DDIT4; GADD45G and down-regulated: KIF3A, AKT1; ABL; JAK1, GLI3 and ALDH1A3. Thus, microarray gene expression analysis can be effective in establishing genes affected in response to FAK inhibitor alone and in response to combination of Y15 with
temozolomide that is important for
glioblastoma therapy.