Yiai Fuzheng decoction inhibits triple-negative breast cancer by remodeling the immune microenvironment.

OBJECTIVE: This study aimed to examine the potential anticancer properties of Yiai Fuzheng decoction (YFD), along with its mechanism of action against triple-negative breast cancer (TNBC). METHODS: A TNBC mouse model was established by inoculating 4T1 cells into the 4th mammary fat pad. Micropositron emission tomography (micro-PET), hematoxylin and eosin (HE) staining, immunohistochemistry, immunofluorescence assays, flow cytometry, and western blotting were used to assess the therapeutic effects of YFD. The components of YFD were identified via UHPLC-Q/Orbitrap MS. Nontargeted metabolomic analysis was performed to identify changes in tumor metabolites via gas chromatography-time-of-flight mass spectrometry (GC-TOF/MS). The Illumina sequencing platform was used to identify differentially expressed genes in the tumors. RESULTS: A total of 20 bioactive components of YFD were screened and identified. We found that YFD treatment resulted in a substantial increase in CD4(+) and CD8(+) T cells, a reduction in myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), and an increase in the M1/M2 ratio of TAMs in tumors. These changes create a tumor-suppressive microenvironment that inhibits tumor growth and metastasis in TNBC mice. YFD can affect various immune regulatory pathways, such as inactivation of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1 and 2 (MEK/ERK1/2) pathway. Additionally, metabolomic analysis suggested that YFD could reprogram several altered metabolic pathways, including the urea cycle; metabolism of arginine and proline; pyruvate; the Warburg effect; D-arginine; and D-ornithine, glutamate, glycine, serine, and tryptophan, to suppress cancer progression. CONCLUSION: Our findings provide preclinical evidence that supports the application of YFD in TNBC treatment.