摘要Objective:To investigate the role of ginsenoside Rd(GRd)in acute myeloid leukemia(AML)cell differentiation.Methods:AML cells were treated with GRd(25,50,100 and 200 μg/mL),retinoic acid(RA,0.1 g/L)and PD98059(20 mg/mL)for 72 h,cell survival was detected by methylthiazolyldiphenyl-tetrazolium bromide and colony formation assays,and cell cycle was detected by flow cytometry.Cell morphology and differentiation were observed by Wright-Giemsa staining,peroxidase chemical staining and cellular immunochemistry assay,respectively.The protein expression levels of GATA binding protein 1(GATA-1),purine rich Box-1(PU.1),phosphorylated-extracellular signal-related kinase(p-ERK),ERK,phosphorylated-glycogen synthase kinase-3β(p-GSK3 β),GSK3β and signal transducer and activator of transcription 1(STAT1)were detected by Western blot.Thirty-six mice were randomly divided into 3 groups using a random number table:model control group(non-treated),GRd group[treated with 200 mg/(kg·d)GRd]and homoharringtonine(HTT)group[treated with 1 mg/(kg·d)HTT].A tumor-bearing nude mouse model was established,and tumor weight and volume were recorded.Changes of subcutaneous tumor tissue were observed after hematoxylin and eosin staining.WT1 and GATA-1 expressions were detected by immunohistochemical staining.Results:The cell survival was inhibited by GRd in a dose-dependent manner and GRd caused G0/G1 cell arrest(P＜0.05).GRd treatment induced leukemia cell differentiation,showing increased expressions of peroxidase and specific proteins concerning erythrogenic or granulocytic differentiation(P＜0.05).GRd treatment elicited upregulation of p-ERK,p-GSK-3β and STAT1 expressions in cells,and reversed the effects of PD98059 on inhibiting the expressions of peroxidase,GATA-1 and PU.1(P＜0.05).After GRd treatment,tumor weight and volume of mice were decreased,and tumor cells underwent massive apoptosis and necrosis(P＜0.05).WT1 level was decreased,and GATA-1 level was significantly increased in subcutaneous tumor tissues(P＜0.05 or P＜0.01).Conclusion:GRd might induce the differentiation of AML cells via regulating the ERK/GSK-3 β signaling pathway.