摘要
Multiple myeloma(MM)is a plasma cell malignancy and remains incurable as it lacks effective curative approaches;thus,novel therapeutic strategies are desperately needed.The study aimed to explore the therapeutic role of dihydromyricetin(DHM)in MM and explore its mechanisms.Human MM and normal plasma samples,human MM cell lines,and normal plasma cells were used for in vitro experiments.Cell counting kit-8(CCK-8),flow cytometry,and trans-well assays were performed for the assessment of cell viability,apoptosis,migration,and invasion,respectively.Quantitative real-time polymerase chain reaction(qRT-PCR)was employed to assess the mRNA expression of signal transducer and activator of transcription 1(STAT1)and retinoic acid-inducible gene I(RIG-I).Western blotting was employed to assess E-cadherin,N-cadherin,signal transducer,STAT1,p-STAT1,and RIG-I protein expression.A tumor xenograft model was used for in vivo experiments.Here,dihydromyricetin(DHM)dose-dependently restrained viability,apoptosis,migration,and invasion,and facilitated apoptosis of U266 cells.After DHM treatment,the Ecadherin level was increased and the N-cadherin level was decreased in U266 and RPMI-8226 cells,suggesting the inhibitory effects of DHM on epithelial-mesenchymal transition(EMT)in MM.Besides,the levels of p-STAT1/STAT1 and RIG-I were down-regulated in MM.However,the STAT1 inhibitor fludarabine undid the suppressive effect of DMH on the malignant characteristics of U266 cells.Also,DHM inhibited MM tumor growth and EMT,and activated STAT1/RIG-I pathway in vivo.Collectively,this study first revealed that DHM can restrain EMT and tumor growth in MM by activating STAT1/RIG-I signaling,which provides a novel drug for the treatment of MM.
基金
The authors disclosed receipt of the following financial support for the research,authorship,and/or publication of this article:This work was supported by Mechanism of Dihydromyricetin Inhibiting Multiple Myeloma Growth and Epithelial Mesenchymal Transition by Regulating STAT1/RIG-I Pathway(Grant Number 2022KY094).
