Objective    To analyze the apoptosis mechani

sms of K562 cells in a PI

3

K-AKT-dependent manner.    Methods    K562 cells were cultured in vitro for experiments below: the proliferation assay of K562 cells detected by MTT

the analysis of apoptosis rate and cell cycle of K562 cells measured by flow cytometry (FCM)

the construction of chronic myeloid leukemia (CML) animal model through the subcutaneous inoculation of K562 cells to 12 BALB/c-nu/nu nude mice

the early apoptosis changes of K562 cells detected by TdT-mediated dUTP nick end labeling (TUNEL) and the in vitro and in vivo changes of N-ras

PI

3

K

AKT1

IKK-β

NF-κB1 at transcription level detected by RT-PCR.    Results    Simvastatin inhibited the proliferation of K562 cells and induced their G

0

/G

1

arrest and significant apoptosis. N-ras and most genes of PI

3

K-AKT signal pathway were expressed differentially in vitro. K562 cells on nude mice could be induced to apoptosis by simvastatin and the apoptotic index increased with the dose accumulation of simvastatin (P=0.000). The differential  mRNA expression changes of N-Ras and most genes of PI

3

K-AKT signal pathway in K562 cells were observed after treatment of simvastatin at different doses (P=0.000 or P=0.003). However

  mRNA expression of the genes in PI

3

K-AKT pathway in vitro differed to that in vivo.    Conclusion    The differential expression at transcription levels of N-ras and the most genes in PI

3

K-AKT pathway that are involved in anti-apoptosis in K562 cells

to some degree

indicates that simvastatin can induce the apoptosis of K562 cells in a PI3K-AKT pathway-dependent fashion in vitro. The animal experiments confirm that there are different mechanisms of simvastatin in inducing the apoptosis of K562 cells in vitro and in vivo.