PARP inhibition increases sensitivity to cisplatin in non-small-cell lung carcinoma via the induction of TET-dependent hydroxymethylation.

ABSTRACT:

Introduction

Platinum-based chemopotentiation by poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) has been confirmed in some non-small-cell lung carcinoma (NSCLC) models, but the molecular mechanisms of PARPi synergy with chemotherapeutics remain poorly clarified. This study aimed to evaluate the efficacy of PARPi niraparib in mitigating resistance to cisplatin through increased ten-eleven translocation (TET) enzymatic activity and 5-hydroxymethylcytosine (5hmC) level in human NSCLC model.

Methods

The chemosensitivity of human NSCLC, sensitive and multidrug-resistant (NCI-H460 and NCI-H460/R, respectively), lung adenocarcinoma cell line (A549), and normal embryonic lung fibroblasts (MRC-5) to increasing concentrations of cisplatin was studied by the MTT assay. The MTT

SUBMITTER: Grdovic N 

PROVIDER: S-EPMC12592190 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature