胶质瘤条件培养基促进巨噬细胞糖酵解及表型转化OACSTPCD

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.