Antonia Göke1, Rüdiger Göke2, Andrea Ofner3, Andreas Herbst3, Brigitte Lankat-Buttgereit4. 1. Research Unit of Gastroenterology, Center for Tumor and Immunobiology, Faculty of Medicine, University of Marburg, Marburg, Germany. 2. Diabetes Center Marburg, Marburg, Germany. 3. Medical Clinic 2, LMU University Hospital Munich, Munich, Germany. 4. Research Unit of Gastroenterology, Center for Tumor and Immunobiology, Faculty of Medicine, University of Marburg, Marburg, Germany lankatbu@staff.uni-marburg.de.
Abstract
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. Copyright
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. Copyright
Authors: Leisl M Packer; Samantha J Stehbens; Vanessa F Bonazzi; Jennifer H Gunter; Robert J Ju; Micheal Ward; Michael G Gartside; Sara A Byron; Pamela M Pollock Journal: Mol Oncol Date: 2019-01-18 Impact factor: 6.603
Authors: Sylvia Grünewald; Oliver Politz; Sebastian Bender; Mélanie Héroult; Klemens Lustig; Uwe Thuss; Christoph Kneip; Charlotte Kopitz; Dieter Zopf; Marie-Pierre Collin; Ulf Boemer; Stuart Ince; Peter Ellinghaus; Dominik Mumberg; Holger Hess-Stumpp; Karl Ziegelbauer Journal: Int J Cancer Date: 2019-03-13 Impact factor: 7.396