Objective:

2

To investigate the role of ginsenoside Rd (GRd) in acute myeloid leukemia (AML) cell differentiation.

Methods:

2

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:

2

The cell survival was inhibited by GRd in a dose-dependent manner and GRd caused G

0

/G

1

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 STAT

1 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:

2

GRd might induce the differentiation of AML cells via regulating the ERK/GSK-3β signaling pathway.