TY - JOUR T1 - The FGFR Inhibitor NVP-BGJ398 Induces NSCLC Cell Death by Activating Caspase-dependent Pathways as well as Caspase-independent Apoptosis JF - Anticancer Research JO - Anticancer Res SP - 5873 LP - 5879 VL - 35 IS - 11 AU - ANTONIA GÖKE AU - RÜDIGER GÖKE AU - ANDREA OFNER AU - ANDREAS HERBST AU - BRIGITTE LANKAT-BUTTGEREIT Y1 - 2015/11/01 UR - http://ar.iiarjournals.org/content/35/11/5873.abstract N2 - Background: Fibroblast growth factor receptors are expressed in diverse cell types. They play a critical role in tumor development. Their activation promotes cell-cycle progression, angiogenesis, and cell survival by induction/suppression of the expression of proteins involved. Materials and Methods: Non-small cell lung cancer (NSCLC) cells (line H1581) were treated with NVP-BGJ398 to evaluate effects on growth by western blot, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and cell-cycle analysis. Results: NVP-BGJ398 induced cell death in H1581 cells by activating caspase-dependent mitochondrial and non-mitochondrial pathways. Caspase-independent apoptosis was also activated. Cells were found to be arrested in the G0/G1 phase. Furthermore, the expression of the tumor-suppressor gene programmed cell death 4 (PDCD4) was up-regulated with suppression of angiopoietin 2 (ANG2). This represents an additional mechanism by which NVP-BGJ389 inhibits tumor growth. Conclusion: Various pathways induce apoptosis in NSCLC cells by employing NVP-BGJ398. These data reflect the potential of cancer treatment utilizing small FGFR inhibitors. ER -