基础医学与临床2024，Vol.44Issue(5)：599-605,7.DOI:10.16352/j.issn.1001-6325.2024.05.0599
胶质瘤条件培养基促进巨噬细胞糖酵解及表型转化
Glioma conditioned medium promotes glycolysis and phenotypic transformation in macrophages
摘要
Abstract
Objective To explore the effects and mechanisms involved in glioma conditioned medium for inducing glycolysis and oncogenic mediators in macrophages.Methods Bone marrow derived macrophage(BMDM)in-duced by hypoxia and mouse glioma cell line GL261 conditioned medium(GCM)(GCM-BMDM)were used as a model.The mRNA level of M1 and M2 oncogenic mediators,hypoxia-inducible factor-1α(HIF-1α)and glycoly-sis associated genes in GCM-BMDM were detected by qPCR.The extracellular acidification rate(ECAR)of GCM-BMDM was detected by Seahorse bioenergy assay method.The protein levels of signal transducer and activa-tor of transcription 6(STAT6),signal transducer and activator of transcription 3(STAT3)and their phosphorylated forms p-STAT6 and p-STAT3 were examined by Western blot.Results GCM stimulated mRNA expression of Hif-1α and a variety of M1 and M2 oncogenic mediators in BMDM(P＜0.01).GCM upregulated the mRNA expres-sion of multiple glycolysis associated genes(P＜0.01)and increased glycolysis level in BMDM(P＜0.001).The glycolysis level was reduced by incubation with lactate dehydrogenase inhibitor stiripentol(STP)(P＜0.05).STP down-regulated mRNA levels of Hif-1α and oncogenic mediators Il-1β,Il-6,Ido and Cd163 in GCM-BMDM(P＜0.01).STP decreased the ratio of p-STAT3/STAT3 and p-STAT6/STAT6 in GCM-BMDM(P＜0.05).Conclusions GCM increases glycolysis level and induces the pro-tumoral phenotypes in GAMs through promoting transcriptional regulation mediated by HIF-1α,STAT3 and STAT6.STP can effectively reduce glycolysis and tran-scriptional expression of oncogenic mediators in GAMs.关键词
胶质瘤相关巨噬细胞/糖酵解/乳酸脱氢酶抑制剂Key words
glioma associated macrophage/glycolysis/lactate dehydrogenase inhibitor分类
医药卫生引用本文复制引用
张迪雅,李云帆,郭泓江,仇佳星,王钰铖,鞠瑞,郭磊..胶质瘤条件培养基促进巨噬细胞糖酵解及表型转化[J].基础医学与临床,2024,44(5):599-605,7.基金项目
国家自然科学基金(82002094) （82002094）
北京市自然科学基金(7222254) （7222254）
中国医学科学院医学与健康科技创新工程(2022-I2M-2-002) （2022-I2M-2-002）
