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.
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*

[Objective]To investigate the effect of Baoyuan Jiedu Decoction(BJD)on serum lipids and white adipose tissue browning in cancer cachexia mice.[Methods]The specific pathogen free C57BL/6 mice were divided into normal group,model group,BJD group and megestrol acetate(MA)group.After 21 days of intervention,the changes of body weight,food intake,water consumption and tumor volume of the mice were observed,multidimensional mass spectrometry-based shotgun lipidomics(MDMS-SL)was used to determine the content of serum lipid of mice,white adipose tissue morphology and lipid droplet area were detected by hematoxylin-eosin(HE)staining,the expressions of white adipose tissue browning related genes were detected by Real-time quantitative polymerase chain reaction(Real-time PCR);and the protein expression of uncoupling protein 1(UCP1)was detected by Western blot and immunohistochemistry(IHC)staining.[Results]Compared with model group,the mice in BJD group were generally in good condition,and their food intake,water consumption and weight were increased significantly(P＜0.05),and the volumes of tumors were significantly suppressed(P＜0.05).Compared with normal group,there were 61 kinds of abnormal lipids in the serum of model group,while 30 kinds of lipids were influenced by BJD treatment(P＜0.05).Compared with model group,BJD alleviated the mass loss and lipid droplets(P＜0.05),inhibited the mRNA expression of UCP1,Cidea,Prdm16(P＜0.05)and the protein expression of UCP1(P＜0.05)in epididymal white adipose tissue(eWAT)and inguinal white adipose tissue(iWAT)of cancer cachexia mice.[Conclusion]BJD can inhibit weight loss,relieve the disorder of serum lipid,and inhibit the white adipose tissue browning of iWAT and eWAT of cancer cachexia mice.