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

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines Pub Date : 2025-07-01 DOI:10.1016/S1875-5364(25)60912-5

Qianyu Bi , Mengran Wang , Li Luo , Beiying Zhang , Siyuan Lv , Zengna Wang , Xuming Ji

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引用次数: 0

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.

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文霞长补方通过拮抗调节CCL18抑制tam诱导的上皮-间质转化，从而抑制NSCLC转移

我们前期研究表明，文霞长补方（WCF）作为一种新辅助疗法，可以抑制肿瘤微环境中M2巨噬细胞的浸润，防止肺癌转移。考虑到肿瘤相关巨噬细胞（tam）在上皮-间质转化（EMT）中的作用，本研究探讨了WCF是否通过减弱tam诱导的非小细胞肺癌（NSCLC）细胞的EMT来阻碍肺癌转移。通过添加或不添加WCF的共培养模型，我们观察到WCF下调巨噬细胞中CD163的表达，降低条件培养基中CCL18的水平，抑制巨噬细胞共培养诱导的非小细胞肺癌细胞的生长、侵袭和EMT。对非小细胞肺癌细胞中CCL18水平和Src过表达的调控表明，WCF的作用是通过CCL18和Src信号传导介导的。在体内，WCF通过阻断Src信号传导抑制重组CCL18 （rCCL18）诱导的裸鼠肿瘤转移。这些发现表明，WCF通过拮抗CCL18抑制tam诱导的EMT，从而抑制NSCLC转移，为其在NSCLC患者中的潜在开发和临床应用提供了证据。

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来源期刊

Chinese Journal of Natural Medicines INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY

CiteScore

7.50

自引率

4.30%

发文量

2235

期刊介绍： The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM). Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.