Inhibition of PI4K IIIα radiosensitizes in human tumor xenograft and immune-competent syngeneic murine tumor model.

ABSTRACT: Phosphatidylinositol (PI) 4-kinase (PI4K) has emerged as a potential target for anti-cancer treatment. We recently reported that simeprevir, an anti-hepatitis C viral (HCV) agent, radiosensitized diverse human cancer cells by inhibiting PI4K IIIα in vitro. In this study, we investigated the radiosensitizing effect of simeprevir in an in vivo tumor xenograft model and the mechanism of its interaction. The immune modulatory effect of PI4K IIIα was evaluated in an immune-competent syngeneic murine tumor model. In in vivo xenograft models using BT474 breast cancer and U251 brain tumor cells, inhibition of PI4K IIIα induced by simeprevir combined with radiation significantly delayed tumor growth compared to either treatment alone. PI4K IIIα inhibition led to eversion of the

SUBMITTER: Park Y 

PROVIDER: S-EPMC5746391 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature