Wenxia Changfu Formula inhibits NSCLC metastasis by halting TAMs-induced epithelial-mesenchymal transition via antagonisticallymodulating CCL18.
10.1016/S1875-5364(25)60912-5
- Author:
Qianyu BI
1
;
Mengran WANG
2
;
Li LUO
1
;
Beiying ZHANG
3
;
Siyuan LV
1
;
Zengna WANG
1
;
Xuming JI
4
,
5
Author Information
1. School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310000, China.
2. Department of Pediatrics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250000, China.
3. Taizhou Enze Medical Center (Group) Enze Hospital, Taizhou 318000, China.
4. School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310000, China. Electronic address: jixuming724@
5. com.
- Publication Type:Journal Article
- Keywords:
Chemokine (C-C motif) ligand 18 (pulmonary and activation-regulated) (CCL18);
Non-small cell lung cancer (NSCLC);
Tumor-associated macrophages;
Tyrosine-protein kinase Src;
Wenxia Changfu Formula
- MeSH:
Epithelial-Mesenchymal Transition/drug effects*;
Carcinoma, Non-Small-Cell Lung/metabolism*;
Humans;
Animals;
Lung Neoplasms/metabolism*;
Chemokines, CC/antagonists & inhibitors*;
Mice;
Mice, Nude;
Drugs, Chinese Herbal/administration & dosage*;
Cell Line, Tumor;
Neoplasm Metastasis;
Tumor-Associated Macrophages/drug effects*;
Mice, Inbred BALB C;
Signal Transduction/drug effects*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(7):838-847
- CountryChina
- Language:English
-
Abstract:
Our previous research 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 tumor-associated macrophages (TAMs) in epithelial-mesenchymal transition (EMT), this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer (NSCLC) cells. Utilizing a co-culture model treated with or without WCF, we observed that WCF downregulated cluster of differentiation 163 (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 recombinant CCL18 (rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling. These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT via antagonistic modulation of CCL18, providing evidence for its potential development and clinical application in NSCLC patients.
