Dataset related to article "Antitumor Activity of a Novel Fibroblast Growth Factor Receptor Inhibitor for Intrahepatic Cholangiocarcinoma."

Fibroblast growth factor receptor 2 (FGFR2) might have an important role in the pathogenesis and biology of cholangiocarcinoma (CCA). We examined FGFR expression in CCA tumor specimens obtained from patients and CCA cell lines, and then determined the effects of the novel FGFR inhibitor, derazantinib (DZB; formally, ARQ 087), which is currently in clinical phase 2 trials for intrahepatic CCA. DZB inhibited the growth of CCA cell lines in a dose-dependent manner, and extracellular signal-regulated kinase 1/2 and AKT. It also activated apoptotic and cell growth arrest signaling. DZB reduced the in vitro invasiveness and the expression of key epithelial-mesenchymal transition genes. The in vitro data correlated with the expression of FGFRs in human CCA specimens by immunohistochemistry (FGFR1, 30% positive; and FGFR2, 65% positive) and the CCA cell lines assayed by Western blot analysis. These correlated in vitro studies suggest that FGFR may play an important role in the pathogenesis and biology of CCA. Our findings support the notion that FGFR inhibitors, like DZB, should be further evaluated at the clinical stage as targeted therapy for CCA treatment.成纤维细胞生长因子受体2（Fibroblast growth factor receptor 2, FGFR2）在胆管癌（cholangiocarcinoma, CCA）的发病机制与生物学进程中或发挥关键作用。本研究检测了患者来源的CCA肿瘤标本及CCA细胞系中的FGFR表达水平，随后评估了新型FGFR抑制剂德扎替尼（derazantinib, DZB；曾用名ARQ 087）的生物学效应——该药物目前正针对肝内胆管癌开展II期临床试验。实验结果显示，DZB可呈剂量依赖性抑制CCA细胞系的增殖，并下调细胞外信号调节激酶1/2（extracellular signal-regulated kinase 1/2, ERK1/2）与AKT的活化水平；同时，其可激活细胞凋亡与细胞生长阻滞相关信号通路。此外，DZB可降低CCA细胞的体外侵袭能力，并下调关键上皮间质转化（epithelial-mesenchymal transition, EMT）相关基因的表达。体外实验数据与免疫组织化学检测的人CCA标本FGFR表达情况（FGFR1阳性率为30%；FGFR2阳性率为65%）及蛋白质印迹分析检测的CCA细胞系FGFR表达水平具有相关性。上述体外相关研究提示，FGFR可能在CCA的发病机制与生物学进程中发挥重要作用。本研究结果支持如下观点：诸如DZB这类FGFR抑制剂，可作为胆管癌靶向治疗药物，在临床阶段开展进一步评估。