Rhodiola rosea L. improves the immunosuppressive microenvironment through the HIF-1α/TGF-β /Smad signaling pathway in breast cancer

Rhodiola rosea L. ( R. rosea ), a traditional Chinese medicinal herb, has gained global attention for its diverse pharmacological activities, especially its anti-tumor effect. While studies have confirmed that R. rosea can hinder the growth of multiple cancer cells, the underlying mechanisms of R. rosea in breast cancer remain elusive. To investigate the anti-breast cancer efficacy and potential mechanism of R. rosea . UPLC-Q/TOF MS was utilized to examine the components of R. rosea . Eight-week-old MMTV-PyMT mice were used to assess the potential impact of R. rosea in breast cancer development. Flow cytometry was performed to evaluate the effectiveness of immune cells in mediating the anti-tumor effects of R. rosea . Additionally, the xCELLigence system aided in examining the proliferation of breast cancer cells after treatment with R. rosea . Furthermore, RNA-seq, RT-qPCR and Western blot were employed to elucidate the underlying mechanism of R. rosea in breast cancer. Lastly, network pharmacology was applied to delve deeper into the primary chemically active components responsible for the pharmacological effects of R. rosea . R. rosea exhibits a substantial effect in curtailing the progression of breast cancer, accomplished by repressing the proliferation of tumor cells and reconfiguring the tumor microenvironment (TME). Mechanistically, R. rosea exerts its anti-tumor effects by downregulating the expression of HIF-1α, TGF-β, and Smad3 in tumor cells, thereby alleviating the hypoxic TME and enhancing immune surveillance. Our study revealed that R. rosea suppressed the development of breast cancer by inhibiting the hypoxic immune microenvironment mediated by the activation of HIF-1α/TGF-β /Smad signaling pathway in tumor cells. These findings, which underscore R. rosea potential as a potent antineoplastic agent, offer a compelling basis for its use as an adjuvant therapy in the treatment of breast cancer.