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Suppression of STAT3 by S31-201 to reduce the production of immunoinhibitory cytokines in a HIF1-α-dependent manner: a study on the MCF-7 cell line

  • Amirhossein Jahangiri
  • Maryam Dadmanesh
  • Khodayar Ghorban
Article

Abstract

Signal transducer and activator of transcription 3 (STAT3) interacts with many gene promoters and transcription factors such as hypoxia-induced factor 1α (HIF-1α). Recent evidences proposed that STAT3 and HIF-1α together are responsible for angiogenesis and immune response suppression. The main aim of this study was to inhibit STAT3 and HIF-1α and assess their effects on the expression of immunosuppressive cytokines. S31-201 and PX-478 were used to inhibit STAT3 and HIF-1α, respectively. In both hypoxic and normoxic conditions, intracellular levels of HIF-1α were evaluated by western blotting and flow cytometry. Supernatant levels were also measured for VEGF, IL-10, and TGF-β concentration. S31-201 suppressed proliferation of MCF-7 cells and led to reduced HIF-1α expression in both hypoxic and normoxic conditions. It also decreased production of the immunosuppressive cytokines. STAT3 inhibition suppressed tumor cell growth and cytokine production in a HIF-1α-dependent manner, and can be used as a promising target in cancer therapies.

Keywords

STAT3 HIF-1α S31-201 VEGF IL-10 TGF-β 

Notes

Acknowledgements

The authors thank Gholamreza Valizade and Sara Shirinzade from Iran University of Medical Science for their suggestions and discussion.

Funding information

This study was supported by a grant from Aja Medical University.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© The Society for In Vitro Biology 2018

Authors and Affiliations

  1. 1.Department of Immunology, School of MedicineAja University of Medical SciencesTehranIran
  2. 2.Department of Infectious Diseases, School of MedicineAja University of Medical SciencesTehranIran

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