Ginsenoside Rd Induces Differentiation of Myeloid Leukemia Cells via Regulating ERK/GSK-3β Signaling Pathway

  • Impact factors: 2.9
  • Publication: Chinese Journal of Integrative Medicine
  • Author:Jiang Yu-xia, Zhao Yan-na, Yu Xiao-ling, Yin Li-ming
  • DOI citation-doi:10.1007/s11655-023-3561-z
  • Date:2023-12-12

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, 0.1g/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-GSK3β), 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-3β signaling pathway.

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