title: SAHA down-regulates the expression of indoleamine 2,3-dioxygenase via             inhibition of the JAK/STAT1 signaling pathway in gallbladder carcinoma cells.
abstract: The aim of the present study was to investigate the role of the JAK/STAT1             signaling pathway in suberoylanilide hydroxamic acid (SAHA)-mediated down-regulation             of indoleamine 2,3-dioxygenase (IDO) in gallbladder carcinoma cells. We treated             SGC-996 gallbladder carcinoma 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 transfection             and reporter gene assay was used for detecting the activation of γ-activated sites             (GAS) and interferon-stimulated response elements (ISRE). The results revealed             that IDO was expressed in SGC-996 cells in a dose- and time-dependent manner when             stimulated with IFN-γ and 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 and SAHA inhibited IFN-γ-induced STAT1 phosphorylation and nuclear translocation.             In addition, SAHA down-regulated IFN-γ-induced activation of GAS and ISRE. In             conclusion, SAHA down-regulated IDO expression via inhibition of the activation             of members of the JAK/STAT1 signaling pathway. Therefore, regulation of the JAK/STAT1             signaling pathway may provide a new gallbladder carcinoma immunotherapeutic strategy             to break tumor immune tolerance.
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Guanmin
authors.initials: G
authors.lastname: Jiang
authors.forename: Jiao
authors.initials: J
authors.lastname: Gao
authors.forename: Lingling
authors.initials: L
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Du
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Jiao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology; D015153:Blotting, Western; D005706:Gallbladder Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D053612:Janus Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D006877:Hydroxamic Acids; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D050794:STAT1 Transcription Factor; D000077337:Vorinostat; D007371:Interferon-gamma; D053612:Janus Kinases