Effects Of Simvastatin On PI3K/Akt And NF-κB Signaling Pathways In Human Acute Myelogenous Leukemia Cell Line

Objective To investigate the effects of3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor,simvatatin(SV), on proliferation, apoptosis, the PI3K/Akt signaling pathway and the NF-κB signaling pathway in human acute myelogenous leukemia cell lines SHI-1and NB4.Methods NB4and SHI-1cells were incubated with different concentration of Simvastatin(5μmol/l、10μmol/l、15μmol/l), taking NB4and SHI-1cells without any treatment as control. Cells of different groups were collected at24h,48h and72h after incubation for further detection. M’IT method was used to assay the growth inhibition rate and flow cytometry was used to detect the early stage apoptosis ratio and cell necrosis ratio. The Human PI3K-Akt and NF-κB Signaling Pathway RT2ProfilerTM PCR Array profiles the expression of genes involved in PI3K-AKT and NF-κB signaling.Results Simvatatin inhibited the proliferation and inducted the apoptosis of SHI-1and NB4cells in time-and dose-dependent manners significantly.(1) The cell growth inhibition rate of NB4cells treated with15μmol/l simvastatin were45.75%,92.91%and96.46%respectively at24h,48h and72h; and the early stage apoptosis ratio were30.25%,64.34%and87.38%, respectively. Compared with the control group,56genes expression levels changed in the group of15umol/L SV at48h, among which,47genes were down-regulated and9genes were up-regulated.(2) The cell growth inhibition rate of SHI-1cells treated with15μmol/l simvastatin were26.82%,47.09%and63.92%respectively at24h,48h and72h; and the early stage apoptosis ratio were5.75%,13.25%and15.59%respectively. Compared with the control group,39genes expression levels changed in the group of15umol/L SV at48h, among which,26genes were down-regulated and13genes were up-regulated.Conclusions Simvatatin potentially inhibit proliferation and induce apoptosis of SHI-1and NB4cells, and the mechanism may be associated with the changes of gene expression levels involved in PI3K-Akt and NF-κB signaling pathway regulated by simvastatin.