Wenxia Changfu Formula inhibits NSCLC metastasis by halting TAMs-induced epithelial-mesenchymal transition via antagonistically modulating CCL18

Our previous studies demonstrated that the Wenxia Changfu Formula (WCF) as a neoadjuvant therapy inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis. Given the role of tumor-associated macrophages (TAMs) in epithelial-mesenchymal transition (EMT), we investigated whether WCF halts lung cancer metastasis by attenuating TAM-induced EMT in NSCLC cells. Using a co-culture model treated with or without WCF, we found that WCF downregulated CD163 expression in macrophages, reduced CCL18 levels in the conditioned medium, and inhibited the growth, invasion, and EMT of NSCLC cells induced by macrophage co-culture. Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF's effects are mediated through CCL18 and Src signaling. In vivo, WCF inhibited rCCL18-induced tumor metastasis in nude mice by blocking Src signaling. These findings suggest that WCF inhibits NSCLC metastasis by halting TAM-induced EMT via antagonistic modulation of CCL18, providing evidence for its future development and clinical application in NSCLC patients.