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
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.
KeywordsSTAT3 HIF-1α S31-201 VEGF IL-10 TGF-β
The authors thank Gholamreza Valizade and Sara Shirinzade from Iran University of Medical Science for their suggestions and discussion.
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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