海南医科大学学报2025，Vol.31Issue(14)：1041-1049,1056,10.DOI:10.13210/j.cnki.jhmu.20241012.002
基于转录组学分析氟维司群治疗对单核-巨噬细胞趋化因子表达及极化的影响
Effects of fulvestrant treatment on chemokine expression and polarization in macrophage cells
摘要
Abstract
Objective:In ER+breast cancer.Tumour-associated macrophages(TAMs)are important components of the breast cancer microenvironment.However,the effects of endocrine therapeutic agents on TAMs is unclear.To investigate the effect of fulvestrant on the polarization of macrophages.Methods:Using THP-1 cell-derived macrophages,we observed changes in macro-phage following fulvestrant stimulation through RT-qPCR,Western blot,and flow cytometry.RNA-Seq was employed to ana-lyze the transcriptomic changes in macrophages induced by fulvestrant.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted to assess the functional roles of these differentially expressed genes.A protein-protein interaction network was constructed to identify hub genes.Finally,the effects of fulvestrant on the expres-sion of five key chemokines among the hub genes were validated using RT-qPCR and a chemokine array.Results:RT-qPCR,Western blot,and flow cytometry analyses revealed that fulvestrant stimulation increased the expression of M2-related markers while decreasing the expression of M1-related markers in macrophages.RNA-Seq results revealed that 118 differentially expressed genes appeared in macrophages stimulated by fulvestrant.GO and KEGG enrichment analyses showed that the differentially ex-pressed genes were enriched in the chemokine-related functions and signalling pathways.Protein-protein interaction network analy-sis and hub gene screening identified five key chemokines(CXCL8,CCL20,CCL22,CXCL10 and CCL7).RT-qPCR showed that the expression trends of these key chemokines were consistent with the RNA-Seq results.Additionally,chemokine array ex-periments confirmed that the secretion of CXCL8,CCL20,and CCL22 by macrophages after fulvestrant stimulation was in-creased,while that of CXCL10 and CCL7 was decreased.Conclusions:The endocrine therapeutic agent fulvestrant was found to promote the expression of the M2-associated macrophage marker CD206 while inhibiting the expression of the M1-associated marker CD86.Additionally,fulvestrant treatment enhanced the secretion of M2-related chemokines and reduced the secretion of M1-related chemokines by macrophages.These findings suggest that fulvestrant treatment promotes macrophage polarization to-wards the M2 phenotype and inhibits polarization towards the M1 phenotype.This shift in macrophage polarization may be associ-ated with the development of resistance to endocrine therapy in clinical settings.关键词
乳腺癌/内分泌治疗耐药/巨噬细胞/趋化因子Key words
Breast cancer/Endocrine resistance/Macrophage/Chemokine分类
医药卫生引用本文复制引用
刘宇婷,杨翠霞,叶敬文,刘泊含,刘鷖雯,何怡青,杜艳,张国良,郭倩,高锋..基于转录组学分析氟维司群治疗对单核-巨噬细胞趋化因子表达及极化的影响[J].海南医科大学学报,2025,31(14):1041-1049,1056,10.基金项目
This study was supported by the National Natural Science Foundation of China(81974445,82273462) 国家自然科学基金资助项目(81974445、82273462) （81974445,82273462）
