Sorafenib alone or as combination therapy for growth control of cholangiocarcinoma

摘要: Abstract Background/aim Treatment options of advanced cholangiocarcinoma (CC) are unsatisfactory and new therapeutic approaches mandatory. Dysregulations the mitogen-activated kinase (MAPK) pathway associated with proliferative advantages tumors commonly observed in CCs. The novel multi-kinase inhibitor sorafenib potently suppresses growth various cancers by inhibiting kinases wild-type B-Raf, mutantV559EB-Raf C-Raf but its effects on CC remains to be explored. We therefore studied antineoplastic potency human cells alone combination conventional cytostatics or IGF-1R inhibition. Methods results Sorafenib treatment dose-dependently blocked growth-factor-induced activation MAPKP inhibited proliferation EGI-1 TFK-1 a time- dose-dependent manner. At least two mechanisms accounted for observed: arrest at G1/G0-transition cell cycle induction apoptosis. was upregulation cyclin-dependent p27Kip1 downregulation cyclin D1. Combining doxorubicin IGF-1R-inhibition resulted (over)additive antiproliferative whereas co-application antimetabolites 5-FU gemcitabine diminished cytostatics. Conclusion Our study demonstrates that can suppressed certain therapies may provide promising rationale future vivo evaluations clinical trials.