Panobinostat Potentiates the Antitumor Efficacy of 5-Fluorouracil in Gastric Cancer by Suppressing Thymidylate Synthase Expression.

ABSTRACT: Resistance to 5-fluorouracil (5-FU), a cornerstone chemotherapy for gastric cancer (GC), is a major clinical obstacle, often driven by the upregulation of its target enzyme, thymidylate synthase (TS). In this study, we investigated the potential of the pan-histone deacetylase inhibitor (HDACi) panobinostat to synergize with 5-FU. In GC cell lines, panobinostat treatment alone suppressed cell viability, clonogenicity, and migration, and this was associated with the induction of G1-phase cell cycle arrest and mitochondria-mediated apoptosis. Crucially, Panobinostat acted synergistically with 5-FU, leading to enhanced cytotoxicity. Mechanistically, 5-FU treatment alone induced a compensatory upregulation of TS protein, a known resistance mechanism. Panobinostat not only suppressed basal TS ex

SUBMITTER: Park S 

PROVIDER: S-EPMC12898101 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature