Salvia miltiorrhiza Bunge aqueous extract inhibits lung metastasis of breast cancer by inhibiting recruitment of M2-like macrophages via CCL2-STAT3 axis

Abstract

The purpose of this study was to evaluate the therapeutic effect of Salvia miltiorrhiza Bunge on breast cancer (BC) metastasis and explore its possible mechanism. The anti-tumor lung metastasis effect of S. miltiorrhiza Bunge aqueous extract (Sme) and tumor-associated macrophages (TAMs) infiltration was observed in 4T1 spontaneous metastasis models. Wound healing and transwell assays assessed the anti-mobility effects of Sme in 4T1 cells and TAMs. Finally, the therapeutic mechanisms of Sme on BC lung metastasis were explored through Hematoxylin-Eosin Staining(HE), enzyme-linked immunosorbent assay (ELISA), network pharmacology and molecular docking, immunohistochemistry (IHC) staining, quantitative real-time PCR (qRT-PCR), and western blotting (WB). Mechanically, Sme was able to reduce the ability of BC cells to recruit macrophages and reduce the release of C-C motif ligand 2 (CCL2). Additionally, WB results show Sme inhibited the p-STAT3 and suppressed the epithelial-mesenchymal transition of the tumor (p < 0.05). In conclusion, S. miltiorrhiza Bunge may lower the incidence of BC. Sme blocks BC cell-macrophage interactions by regulating the CCL2-STAT3 axis, reducing BC cell migration. These findings may form the basis of new treatments for BC progression. Sme blocks BC cell-macrophage interactions by uniquely regulating the CCL2-STAT3 axis. Our research results provide strong pharmacological evidence for the clinical treatment of lung metastasis of BC with S. miltiorrhiza Bunge.

Keywords: Salvia miltiorrhiza Bunge aqueous extract; Breast cancer lung metastases; C-C motif ligand 2; Tumor-associated macrophages.