Göke Antonia, Göke Rüdiger, Ofner Andrea, Herbst Andreas, Lankat-Buttgereit Brigitte
Research Unit of Gastroenterology, Center for Tumor and Immunobiology, Faculty of Medicine, University of Marburg, Marburg, Germany.
Diabetes Center Marburg, Marburg, Germany.
Anticancer Res. 2015 Nov;35(11):5873-9.
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.
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.
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.
Various pathways induce apoptosis in NSCLC cells by employing NVP-BGJ398. These data reflect the potential of cancer treatment utilizing small FGFR inhibitors.
成纤维细胞生长因子受体在多种细胞类型中表达。它们在肿瘤发展中起关键作用。其激活通过诱导/抑制相关蛋白的表达促进细胞周期进程、血管生成和细胞存活。
用NVP-BGJ398处理非小细胞肺癌（NSCLC）细胞（H1581细胞系），通过蛋白质印迹法、3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法和细胞周期分析评估对生长的影响。
NVP-BGJ398通过激活半胱天冬酶依赖性线粒体和非线粒体途径诱导H1581细胞死亡。半胱天冬酶非依赖性凋亡也被激活。发现细胞停滞于G0/G1期。此外，肿瘤抑制基因程序性细胞死亡4（PDCD4）的表达上调，血管生成素2（ANG2）受到抑制。这代表了NVP-BGJ389抑制肿瘤生长的另一种机制。
多种途径通过使用NVP-BGJ398诱导NSCLC细胞凋亡。这些数据反映了利用小分子FGFR抑制剂进行癌症治疗的潜力。
