The anti-cancer effects of itraconazole in epithelial ovarian cancer.

ABSTRACT: We assessed the anti-proliferative activity of itraconazole using an EOC cell line (SKOV3ip1) and endothelial cell lines (HUVEC & SVEC4-10). We also examined angiogenesis (VEGFR2, p-ERK, p-PLCr1/2), hedgehog (Gli1, Ptch1, SMO), and mTOR (pS6K1) signaling pathways to determine the mechanism of action of itraconazole. Furthermore, we evaluated the synergistic effects of itraconazole and paclitaxel using orthotopic mouse models with established EOC cells (SKOV3ip1 or HeyA8) as well as patient-derived xenografts (PDXs). Itraconazole treatment inhibited proliferation of endothelial cells in a dose-dependent manner, but had no effect on EOC cells. The endothelial cell antiproliferative effect was associated with inhibition of hedgehog, and mTOR pathways and angiogenesis. In xenograft models of E

SUBMITTER: Choi CH 

PROVIDER: S-EPMC5529373 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature