SAHA down-regulates the expression of indoleamine 2,3-dioxygenase via inhibition of the JAK/STAT1 signaling pathway in gallbladder carcinoma cells

Zhang,Peng; Jiang,Guanmin; Gao,Jiao; Li,Lingling; Du,Jun; Jiao,Xingyuan

doi:10.3892/or.2012.2073

SAHA down-regulates the expression of indoleamine 2,3-dioxygenase via inhibition of the JAK/STAT1 signaling pathway in gallbladder carcinoma cells

Authors:
- Peng Zhang
- Guanmin Jiang
- Jiao Gao
- Lingling Li
- Jun Du
- Xingyuan Jiao
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Affiliations: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P.R. China, Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Science, Sun Yat-sen University, University Town, Guangzhou 510006, P.R. China, Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, P.R. China
Published online on: October 8, 2012 https://doi.org/10.3892/or.2012.2073
Pages: 269-275

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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.

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