Abstract
BACKGROUND: Breast cancer (BC) is a major health concern among women. SanHuang decoction (SHD), a Chinese herbal formula, has exhibited the potential for clinical application in patients with BC. This study aimed to clarify the mechanism of SHD's action in the treatment of BC based on macrophage function and nuclear factor kappa B (NF-κB) pathway. METHODS: M1 polarized macrophages were cocultured with MDA-MB-231 BC cells, and treated with 10 mg/mL of SHD for 72 hours. Scratch and transwell assays were used to observe the inhibitory effect of SHD, and the levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), IL-1β, cleaved caspase 3, B-cell lymphoma 2 (BCL-2), BCL-2-associated X (BAX), P65, phosphorylated P65 (p-P65), inhibitor of kappa B (IκB), and phosphorylated IκB (p-IκB) were detected via Western blotting. Forty patients with BC were randomly divided into a control group [neoadjuvant chemotherapy (NACT)] and observation group (NACT + SHD). After 9 weeks of treatment, magnetic resonance imaging scans were performed to evaluate the tumor size, and immunofluorescence staining was performed to investigate the effect of SHD on the regulation of M1 macrophages in tumor tissue. RESULTS: SHD inhibited the migration ability of MDA-MB-231 cells, and the effect was significantly enhanced after coculture with M1/THP-1. Western blot results showed that SHD could significantly increase the expression of TNF-α, IL-1β, IL-6, BAX, cleaved caspase 3, p-P65, and p-IκB while decreasing that of BCL-2. In vivo studies showed that SHD could reduce the tumor size and increase the expression of M1 macrophages. CONCLUSIONS: SHD could enhance the expression of M1/THP-1 cytokines, promote the inflammatory response in the tumor microenvironment, and thus inhibit the proliferation of BC and regulate its pathological process, likely through activating NF-κB signaling pathway.