RT Journal Article
SR Electronic
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
FD International Institute of Anticancer Research
SP 5873
OP 5879
VO 35
IS 11
A1 ANTONIA GÖKE
A1 RÜDIGER GÖKE
A1 ANDREA OFNER
A1 ANDREAS HERBST
A1 BRIGITTE LANKAT-BUTTGEREIT
YR 2015
UL http://ar.iiarjournals.org/content/35/11/5873.abstract
AB 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.