Influence of myricetin on immune escape of nasopharyngeal carcinoma cells by regulating JAK-STAT-IRF1 signaling pathway
ZHANG Yujie
LI Jiahui
SI Yuguang
Abstract:Objective To investigate the influence of myricetin on immune escape of nasopharyngeal carcinoma cells and its regulatory effect on Janus kinases(JAK)/signal transducer and activator of transcription(STAT)/interferon regulatory factor 1(IRF1)signaling pathway.Methods In vitro experiment:Human nasopharyngeal carcinoma CNE1 cells were cultured and grouped into control group,myricetin L group,myricetin M group,myricetin H group and myricetin H+ Broussonin E group.MTT assay was applied to detect cell proliferation.Cell apoptosis was detected by Hoechst method.Western blot was applied to verify the protein expressions of fork-like transcription factor 3(Foxp3),retinoid acid receptor related orphan receptor γt(RORγt),phosphorylated(p)-Janus kinase(JAK)1,JAK1,p-JAK2,JAK2,p-STAT 1,STAT1 and IRF1.In vivo experiment:BALB/c nude mice model of nasopharyngeal carcinoma was established and the mice were randomly grouped into model group,low-dose myricetin group,middle-dose myricetin group,high-dose myricetin group and paclitaxel group.Tumor body was collected and weighed.The expression of programmed death receptor 1 ligand(PD-L1)in macrophages was detected by flow cytometry.Western blot was applied to detect the protein expressions of Foxp3,RORγt,p-JAK1,JAK1,p-JAK2,JAK2,p-STAT1,STAT1 and IRF1 in tumor body.Results Compared with the control group,the proliferation ability of CNE1 cells and the protein expressions of RORγt,p-JAK1/JAK1,p-JAK2/JAK2,p-STAT1/STAT1,IRF1 in myricetin L,M and H groups decreased significantly,while the apoptosis rate and the protein expression of Foxp3 increased obviously(P<0.05).Compared with myricetin H group,the proliferation ability of CNE1 cells and the expression of RORγt,p-JAK1/JAK1,p-JAK2/JAK2,p-STAT1/STAT1 and IRF1 proteins in myricetin H + Broussonin E group increased significantly,whereas the apoptosis rate and the expression of Foxp3 protein decreased remarkably(P<0.05).Compared with the model group,the expression of Foxp3 protein increased significantly in low,medium and high dose myricetin groups,while tumor mass and the expression of PD-L1,RORγt,p-JAK1/JAK1,p-JAK2/JAK2,p-STAT1/STAT1 and IRF1 proteins decreased obviously(P<0.05).Conclusion Myricetin may inhibit immune escape of nasopharyngeal carcinoma cells by inhibiting the activation of JAK-STAT-IRF1 signaling pathway.
Keywords:myricetinnasopharyngeal carcinoma cellsJanus kinases(JAK)/signal transducer and activator of transcription(STAT)/interferon regulatory factor 1(IRF1)signaling pathwayimmune escape
Publication Date:2023-12-25
Online Publishing Date:2025-08-15(First online date of this platform, not the publication date of the document)
Pages:5( 3717-3721 )
