Inhibition of histone deacetylases sensitizes EGF receptor-TK inhibitor-resistant non-small-cell lung cancer cells to erlotinib in vitro and in vivo.

ABSTRACT:

Background and purpose

Intrinsic and/or acquired resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) commonly occurs in patients with non-small-cell lung cancer (NSCLC). Here, we developed a combined therapy of histone deacetylase inhibition by a novel HDAC inhibitor, YF454A, with erlotinib to overcome EGFR-TKI resistance in NSCLC.

Experimental approach

The sensitization of the effects of erlotinib by YF454A was examined in a panel of EGFR-TKI-resistant NSCLC cell lines in vitro and two different erlotinib-resistant NSCLC xenograft mouse models in vivo. Western blotting and Affymetrix GeneChip expression analysis were further performed to determine the underlying mechanisms for the effects of the combination of erlotinib and YF454A.

Key

SUBMITTER: Yu W 

PROVIDER: S-EPMC5610149 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature