Ruyong formula improves thymus function of CUMS-stimulated breast cancer mice

Ethnopharmacological relevance: Ruyong Formula (RYF) is a famous Chinese herbal formula composed of 10 traditional Chinese herbs. It has been used as a therapeutic agent for breast cancer patients with depressive symptoms in China. However, its underlying pharmacological mechanism remains unclear.Aim of the study: This study aimed to explore the mechanism of RYF on the changes of thymus immune function in breast cancer body under mood disorders such as depression/anxiety.Materials and methods: The chronic unpredictable mild stress (CUMS) was used to stimulate 4T1 breast cancer mice. The behavioral changes, 5-hydroxytryptamine (5-HT) level in brain, cytokeratin 5 (CK5) and 8 (CK8) expression in thymus, the proportion of T cell subsets, the thymic output, phenotypic changes of thymus epithelial cells (TECs), the expression levels of immune-related factors and downstream proteins of TSLP were analyzed after RYF treatment.Results: In CUMS stimulated group, the level of 5-HT in brain was significantly increased after RYF treatment. The output function of the thymus was improved, and the number of TECs in the medulla (CK5+), the proportion of CD3+CD4-CD8- (Double negative) and CD3+CD4+CD8+ (Double positive) T cells were all increased. The mRNA level of TSLP in mouse thymus was significantly decreased, but increased for IL-7. The protein levels of TSLP and Vimentin were decreased, but increased for p-STAT3, p-JAK2, E-cadherin, and p-PI3K p55 in vivo. In vitro study was showed the levels of Snail 1, Zeb 1 and Smad increased significantly in TGF-beta 1 group, and RYF could reverse their expression.Conclusions: RYF could restore the structure and function of the thymus in depressed breast cancer mice by reversing the phenotypic changes of TECs and activating the JAK2/STAT3/PI3K pathway.

Automated summary

The Ruyong Formula (RYF), a traditional Chinese herbal formula, has been used to treat breast cancer patients with depressive symptoms in China. This study aimed to investigate the pharmacological mechanism of RYF on thymus immune function changes in breast cancer patients with mood disorders.