Babaodan suppresses inflammatory and vascular microenvironment in triple-negative breast cancer by inhibiting the cGAS-STING/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine compound Babaodan (BBD), originating from Ming Dynasty in China, is known for its "clearing heat, removing toxins, circulating blood and transforming stasis" effects. Recent evidence increasingly highlights its potential in tumor treatment. However, its efficacy and underlying pharmacological mechanisms in triple-negative breast cancer (TNBC) remain underexplored.

AIM OF THE STUDY: This study aimed to investigate the therapeutic potential of the traditional Chinese medicine Babaodan (BBD) on the inflammatory and vascular microenvironment in TNBC.

MATERIALS AND METHODS: Using a 4T1 tumor-bearing mouse model, the effects of BBD on tumor inflammatory and vascular microenvironment were evaluated through histopathology, immunofluorescence, and immunohistochemical staining. Furthermore, serum metabolomics was employed to identify the active components and relevant pharmacological mechanisms of BBD in regulating TNBC, with validation performed by Western blot.

RESULTS: Our findings demonstrated that BBD treatment significantly inhibited the activation of cGAS-STING/NF-κB signaling pathway, evidenced by reducing phosphorylation levels of STING, TBK1, IRF3, p65, and IκBα. This led to a sharp decline in downstream inflammatory cytokines, thereby ameliorating the tumor inflammatory microenvironment. Concurrently, BBD also alleviated tumor hypoxia and promoted vascular normalization, restoring intratumoral blood perfusion.

CONCLUSION: These results suggested that BBD exerted its dual anti-tumor effects by suppressing the cGAS-STING/NF-κB signaling pathway, effectively improving the inflammatory and vascular microenvironment in TNBC. This study provides a novel theoretical basis and potential therapeutic strategy for the application of traditional medicine in TNBC treatment.