Fu-Zheng-Yi-Liu Formula inhibits the stem cells and metastasis of prostate cancer via tumor-associated macrophages/C-C motif chemokine ligand 5 pathway in tumor microenvironment  

作　　者：CHEN Chiwei HUANG Renlun WANG Neng ZHENG Yifeng ZHOU Jianfu YANG Bowen WANG Xuan ZHANG Juping PAN Bo CHEN Zhiqiang WANG Shengqi WANG Zhiyu XIANG Songtao 

机构地区：[1]The Research Center of Integrative Cancer Medicine,Discipline of Integrated Chinese and Western Medicine,the Second Clinical College of Guangzhou University of Chinese Medicine,Guangzhou 510000,China [2]The First Clinical College of Guangzhou University of Chinese Medicine,Guangzhou 510000,China [3]Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome,Guangdong Provincial Academy of Chinese Medical Sciences,Guangdong Provincial Hospital of Chinese Medicine,Guangzhou 510000,China [4]Guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease Research,Guangzhou University of Chinese Medicine,Guangzhou 510000,China [5]The Research Center for Integrative Medicine,School of Basic Medical Sciences,Guangzhou University of Chinese Medicine,Guangzhou 510000,China [6]State Key Laboratory of Dampness Syndrome of Chinese Medicine,The Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510000,China

出　　处：《Chinese Journal of Natural Medicines》2024年第6期501-514,共14页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.82274512);Guangzhou Science and Technology Project(No.202201020327);Collaborative basic and clinical Innovation project between Guangdong Hospital of Chinese Medicine and the School of Biomedical Sciences of the Chinese University of Hong Kong(No.YN2018HK02);Guangdong basic and Applied basic Research Fund(No.2023A1515110708).

摘　　要：Prostate cancer(PCa)is the second most common malignancy among men globally.The Fu-Zheng-Yi-Liu(FZYL)Formula has been widely utilized in the treatment of PCa.This study investigates whether the FZYL Formula can inhibit PCa by tar-geting the TAMs/CCL5 pathway.We conducted in vitro co-cultures and in vivo co-injections of PCa cells and TAMs to mimic their in-teraction.Results showed that the FZYL Formula significantly reduced the proliferation,colony formation,subpopulations of PCSCs,and sphere-formation efficacy of PCa cells,even in the presence of TAM co-culture.Additionally,the Formula markedly decreased the migration,invasion,and epithelial-mesenchymal transition(EMT)of PCa cells induced by TAMs.The FZYL Formula also reversed M2 phenotype polarization in TAMs and dose-dependently reduced their CCL5 expression and secretion,with minimal cytotoxicity observed.Mechanistic studies confirmed that the TAMs/CCL5 axis is a critical target of the FZYL Formula,as the addition of exogen-ous CCL5 partially reversed the formula’s inhibitory effects on PCSCs self-renewal in the co-culture system.Importantly,the Formula also significantly inhibited the growth of PCa xenografts,bone metastasis,and PCSCs activity in vivo by targeting the TAMs/CCL5 pathway.Overall,this study not only elucidates the immunomodulatory mechanism of the FZYL Formula in PCa therapy but also highlights the TAMs/CCL5 axis as a promising therapeutic target.

关 键 词：Traditional Chinese medicine Tumor-associated macrophages Prostate cancer stem cells CCL5 Tumor microenvironment 

分 类 号：R965[医药卫生—药理学]