Yin Xiangjun, Sun Xiaohui, Li Aoxiang, Ruan Jiazhao, Niu Hongxia, Zhou Yuan, Chen Guang, Guo Jianbo, He Qingyong, Ji Xuming
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.
School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China.
J Ethnopharmacol. 2025 Jul 24;351:120103. doi: 10.1016/j.jep.2025.120103. Epub 2025 Jun 6.
Wenxia Changfu formula (WCF), a traditional Chinese herbal medicine, has shown therapeutic potential for treating lung cancer in clinical practice. Metastasis is the main cause of mortality in lung cancer patients, reprogramming tumor-associated macrophages (TAMs) represents a promising strategy.
This study aims to investigate the effects of WCF on metastasis of Lewis lung cancer (LLC) cells and to elucidate the underlying mechanisms.
RAW264.7 cells were differentiated into M2 macrophages, and conditioned medium from macrophages with different interventions was used to culture LLC cells. The effects of WCF on tumor migration and invasion were evaluated. Specific markers of macrophage polarization, non-targeted metabolomics, lipid content, and the PPAR-γ/CD36 pathway in macrophages were analyzed. To investigate the in vivo effects of WCF on metastasis, a mouse model was established using LLC-luciferase (LLC-Luc) cells, macrophages were depleted upon clodronate liposome administration.
WCF effectively inhibited M2-like polarization of macrophages, as evidenced by reduced expression of CD206 and Arg-1, while promoting M1-like polarization, with increased expression of CD86, IL-1β, and TNF-α. These changes were correlated with decreased migration and invasion of LLC cells. In vivo, WCF treatment significantly decreased the fluorescence intensity of LLC-Luc cells, with no significant difference observed between WCF and clodronate liposome interventions. Furthermore, WCF regulated fatty acid metabolism, decreased lipid accumulation, and suppressed the PPAR-γ/CD36 pathway in M2 macrophages.
WCF inhibits the metastasis of LLC cells by reprogramming TAMs, mediated by the PPAR-γ/CD36 pathway and fatty acid metabolism.
温夏长福方（WCF）是一种传统中药，在临床实践中已显示出治疗肺癌的潜力。转移是肺癌患者死亡的主要原因，重编程肿瘤相关巨噬细胞（TAM）是一种有前景的策略。
本研究旨在探讨WCF对Lewis肺癌（LLC）细胞转移的影响，并阐明其潜在机制。
将RAW264.7细胞分化为M2巨噬细胞，并用不同干预措施处理后的巨噬细胞条件培养基培养LLC细胞。评估WCF对肿瘤迁移和侵袭的影响。分析巨噬细胞极化的特异性标志物、非靶向代谢组学、脂质含量以及巨噬细胞中的PPAR-γ/CD36途径。为研究WCF在体内对转移的影响，使用LLC-荧光素酶（LLC-Luc）细胞建立小鼠模型，给予氯膦酸脂质体后清除巨噬细胞。
WCF有效抑制巨噬细胞的M2样极化，表现为CD206和Arg-1表达降低，同时促进M1样极化，CD86、IL-1β和TNF-α表达增加。这些变化与LLC细胞迁移和侵袭减少相关。在体内，WCF治疗显著降低了LLC-Luc细胞的荧光强度，WCF与氯膦酸脂质体干预之间未观察到显著差异。此外，WCF调节脂肪酸代谢，减少脂质积累，并抑制M2巨噬细胞中的PPAR-γ/CD36途径。
WCF通过重编程TAM抑制LLC细胞转移，由PPAR-γ/CD36途径和脂肪酸代谢介导。
