Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis.

ABSTRACT: Resminostat, a novel class I, IIb, and IV histone deacetylase inhibitor, was studied in advanced hepatocellular carcinoma (HCC) patients after relapse to sorafenib (SHELTER study). In this phase I/II clinical trial, combination of sorafenib and resminostat was safe and showed early signs of efficacy. However, the molecular mechanisms behind this synergism have not been explored yet. In this work, we aimed to analyze whether resminostat regulates epithelial-mesenchymal and stemness phenotype as a mechanism of sensitization to sorafenib. Three HCC cell lines with differences in their epithelial/mesenchymal characteristics were treated with resminostat and sorafenib alone, or in combination. Resminostat prevented growth and induced cell death in the HCC cells, in a time and dose dependent man

SUBMITTER: Soukupova J 

PROVIDER: S-EPMC5746389 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature