The Antitumor and Immunomodulatory Effect of Yanghe Decoction in Breast Cancer Is Related to the Modulation of the JAKSTAT Signaling Pathway

Abstract EN

Background.

Yanghe decoction (YHD) has been used in the treatment of breast cancer for hundreds of years in Asia.

However, the underlying mechanisms are currently unknown.

The present study aims to evaluate the efficacy of YHD on antitumor and immune system enhancement in a 4T1 mouse breast cancer model and to clarify the antitumor mechanisms of YHD in breast cancer.

Materials and Methods.

The YHD was orally administrated for 2 weeks after inoculation.

Tumor tissues were then removed, weighed, and homogenized.

Flow cytometry was used to detect the number of Myeloid-Derived Suppressor Cells (MDSCs), Natural Killer T Cells (NKTs), and T cell subsets.

Quantitative real-time PCR was used to detect the expression of inducible nitric oxide synthase (iNOS) and arginase-1 (ARG-1).

Western blot was used to detect the protein expression of signal transducers and the activator of transcription 1 (STAT1), phosphorylated-signal transducers and the activator of transcription 1 (p-STAT1), signal transducers and the activator of transcription 3 (STAT3), and phosphorylated-signal transducers and the activator of transcription 3 (p-STAT3).

The expression levels of interleukin-6 (IL-6), transforming growth factor-β (TGF-β), and interferon-γ (IFN-γ) were detected using an enzyme linked immunosorbent assay.

Results.

We found that the tumor weight of YHD high-dose group was significantly lower compared with the control group (p<0.05).

The YHD depressed the expression of MDSCs, iNOS, ARG-1, IL-6, TGF-β, and p-STAT3 and significantly increased the expression of IFN-γ, NKTs, CD4+ T cells, and p-STAT1.

Conclusion.

Our results showed that The mechanisms of YHD inhibit 4T1 breast tumor growth may be related to downregulating the expression of iNOS and ARG-1, negatively regulating the Janus kinase/STAT3 (JAK/STAT3) pathway by repressing the expression of IL-6 and TGF-β.

Meanwhile, YHD enhances the immune capacity via increasing the expression of NKTs, CD4+ T cells, IFN-γ, and p-STAT1.