Wenxia Changfu Formula inhibits NSCLC metastasis by halting TAMs-induced epithelial-mesenchymal transition via antagonistically modulating CCL18
摘要Our previous research demonstrated that the Wenxia Changfu Formula(WCF),as a neoad-juvant therapy,inhibits M2 macrophage infiltration in the tumor microenvironment and pre-vents lung cancer metastasis.Given tumor-associated macrophages(TAMs)in epithelial-mes-enchymal transition(EMT),this study investigated whether WCF impedes lung cancer meta-stasis 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 condi-tioned medium,and inhibited the growth,invasion,and EMT of NSCLC cells induced by mac-rophage co-culture.Manipulation of CCL18 levels and Src overexpression in NSCLC cells re-vealed that WCF's effects are mediated through CCL18 and Src signaling.In vivo,WCF inhib-ited recombinant CCL18(rCCL18)-induced tumor metastasis in nude mice by blocking Src sig-naling.These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-in-duced EMT via antagonistic modulation of CCL18,providing evidence for its potential devel-opment and clinical application in NSCLC patients.
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