AP-1抑制剂联合硼替佐米调控IRF4/MYC轴对多发性骨髓瘤小鼠模型的影响OA

Objective To investigate the effect and underlying mechanism of activator protein-1(AP-1)inhibitor T-5224 combined with bortezomib(BTZ)in multiple myeloma(MM)mice xenograft mice.Methods Twelve nonobese diabetic/severe combined immunedeficiency(NOD/SCID)mice were randomly divided into four groups with 3 mice per group,including control group,T-5224 group,BTZ group,and T-5224+BTZ group.All agents were administered via intraperitoneal injection.The MM mouse model was treated with AP-1 inhibitor T-5224 combined with BTZ.Terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling(TUNEL)staining was performed to observe tumor cell apoptosis.qRT-PCR was used to detect the expression levels of related genes.Immunohistochemistry and Western blot were adopted to measure the protein levels of interferon regulatory factor 4(IRF4),MYC,as well as apoptotic markers cleaved caspase 3 and cleaved PARP in mouse tumor tissues.Results After 14 days treatment,compared with the control group,T-5224 group and BTZ group,the T-5224+BTZ group exhibited significantly decreased relative mRNA and protein expressions of JunB,IRF4 and MYC(P<0.05),while the expression of proapoptotic proteins cleaved caspase 3 and cleaved-PARP was markedly increased,with statistically significant differences(P<0.05).Conclusion The AP-1 inhibitor T-5224 combined with BTZ inhibits IRF4/MYC axis in vivo,and the combi-nation of the two drugs would exert a synergistic effect.