Suberoylanilide hydroxamic acid (SAHA) suppresses JAK/STAT1 signal pathway to down-regulate the expression of indoleamine 2, 3-dioxygenuse in gallbladder carcinoma cells / 中华肝胆外科杂志

ABSTRACT

Objective To investigate the mechanism on JAK/STAT1 signal pathway in SAHA down-regulation of indoleamine 2,3-dioxygenase (IDO) in gallbladder carcinoma cells.MethodsWe treated gallbladder carcinoma SGC-996 cells with IFN-γ and SAHA.Western blotting was used to detect the expression of IDO,signal transducer and activator of transcription 1 (STAT1) phosphorylation and interferon regulatory factor genes-1 (IRF-1).Confocal microscopy analysis was used to detect STAT1 translocation.Transient transfections and reporter genes assay was used in detecting the activation of γ-activated sites (GAS) and interferon stimulated response elements (ISRE).ResultsIDO expressed in SGC-996 cells in dose- and time-dependent manners when stimulated with IFN-γ.SAHA down-regulated the expression of IDO induced by IFN-γ in a dose-dependent manner.SAHA blocked the expression of IRF-1 induced by IFN-γ.SAHA inhibited the IFN-γ-induced STAT1 phosphorylation and nuclear translocation.SAHA down-regulated IFN-γ-induced activation of GAS and ISRE.ConclusionsSAHA may down-regulate IDO expression through inhibiting the activation of members in JAK/STAT1 signal pathway.This may provide a new immunotherapeutic strategy to break tumor immune tolerance in gallbladder carcinoma.