Antifibrotic activity of sorafenib in experimental hepatic fibrosis: refinement of inhibitory targets, dosing, and window of efficacy in vivo.

ABSTRACT:

Background

Sorafenib, which is approved for treatment of HCC, has also shown promising antifibrotic activity, and therefore refinement of its dosing requirements and window of efficacy are important goals prior to antifibrotic clinical trials.

Aim

The purpose of this study was to determine the minimal effective dose and optimal timing of sorafenib therapy in cultured human stellate cells and in rats with experimental hepatic fibrosis.

Methods

Effects of sorafenib were assessed in a human stellate cell line (LX-2). In vivo, rats were treated for 8 weeks with TAA three times per week (150 mg/kg IP), and with either PBS or sorafenib administered daily at doses of 1.25, 5 or 7 mg/kg/day gavage either at the beginning of TAA administration for 8 weeks, during weeks 4-8, or

SUBMITTER: Hong F 

PROVIDER: S-EPMC3543488 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature