Effect of Atorvastatin on apoptosis of HL-60 leukemic cells via the regulation of the phosphatidylinositol 3-kinase/serine/threonine protein kinase/mammalian target of rapamycin signaling pathway / 中华实用儿科临床杂志

ABSTRACT

Objective To investigate the effect of Atorvastatin on the proliferation and apoptosis of leukemic HL-60-cell line,and to explore the possible role of phosphatidylinositol 3-kinase/serine/threonine protein kinase /mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway in this process.Methods HL-60 cells were incubated with different concentrations of Atorvastatin (1,5,10 μmol/L),and HL-60 cells without any treatment were used as controls.The proliferation of HL-60 which was investigated by four methyl thiazolyl tetrazolium assay when cells were cultured for 12,24,48 hours.The apoptosis was detected by flow cytometry after cells were incubated for 48 hours.The mRNA and protein expressions of AKT,PI3K and mTOR were detected by reverse transcription-polymerase chain reaction and Western blot methods,respectively.Results The results indicated that Atorvastatin could inhibit the proliferation and induce the apoptosis of HL-60 cells.When treated with 10 μmol/L Atorvastatin after 48 h,the proliferation inhibition of HL-60 was observed most obviously,with a high rate of (39.77 ± 3.01) ％,compared with the control group,it had statistical significance (t =4.016,P ＜ 0.01),meanwhile,the apoptosis of HL-60 was most notable,at a rate of (43.29 ±3.91)％,compared with the control group,it had statistical significance (t =3.625,P ＜ 0.05).There were basal expression of AKT,PI3K and mTOR in the control group.When treated with 10 μmol/L Atorvastatin after 48 h,the mRNA expression of PI3K,AKT and mTOR were down-regulated most obviously,at a decrease of (37.05 ± 4.11) ％,(53.79 ± 3.27) ％,(40.63 ± 2.42) ％ (t =4.805,3.799,4.312,all P ＜ 0.05),respectively,in comparison with the control group.At the same condition,the protein expression of PI3K,AKT and mTOR were decreased most visibly,with a decline of (41.09 ± 3.17) ％,(45.67 ± 2.92) ％,(63.41 ± 3.59) ％ (t =3.576,4.727,4.902,all P ＜ 0.05) respectively in comparison with the control group.Conclusions Atorvastatin can inhibit the proliferation and induce the apoptosis of leukemic cell HL-60,and the mechanism may be associated with the PI3K/ AKT/mTOR signal pathway.