title: Study on the function and mechanism of atorvastatin in regulating leukemic cell apoptosis by the PI3K/Akt pathway.
abstract: OBJECTIVE
  To investigate the effects of atorvastatin on the proliferation and apoptosis of leukemic cell lines (Jurkat, K562 and HL-60), and expore the function of TLR4/MYD88/NF-κB and PI3K/AKT signal pathway in this process.
  
  
  METHODS
  Cells in logarithmic growth phase were divided into negative control group and experimental group (cells were treated with atorvastatin with intervention concentrations of 1, 5 and 10 μmol/L respectively) and cultured for 24 hours. Changes in apoptosis and cell cycle of leukemic cells were detected utilizing the Flow Cytometry. Changes in the expression of TLR4/MYD88/NF-κB and PI3K/AKT signal pathway related genes were detected utilizing Real-time PCR and Western Blot method.
  
  
  RESULTS
  Atorvastatin inhibit proliferation and induce apoptosis in K562, HL-60 and Jurkat cells in a dose-dependent manner. K562, HL-60 and Jurkat cells in G0/G1 phase increased and that in S phase decreased after being treated with atorvastatin for 24 hours compared with that in control group, suggesting that the atorvastatin can retard the three cells in the G0/G1 phase. The study find that the basal expressions of TLR4, MYD88 and NF-κB gene in K562, HL-60 and Jurkat cells are obviously down-regulated in a dose-dependent manner after being treated with atorvastatin with different concentrations. This down-regulation action of atorvastatin to the expression of the TLR4, MYD88 and NF-κB gene becomes more obvious with the increase of the drug level. In addition, the PI3K, AKT and their phosphorylation levels in the above cells down-regulate obviously in a dose-dependent manner after being treated with atorvastatin. This down-regulation action of atorvastatin to the PI3K, AKT and their phosphorylation levels become more obvious with the increase of the drug level.
  
  
  CONCLUSIONS
  Atorvastatin can inhibit proliferation and induce apoptosis in leukemia cells, which may be associated with the regulation of atorvastatin to the TLR4/MYD88/PI3K/AKT/NF-κB signaling pathway.
authors.affiliation: Department of Paediatrics, Renmin Hospital, Wuhan University Wuhan 430060, Hubei Province, P.R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Paediatrics, Renmin Hospital, Wuhan University Wuhan 430060, Hubei Province, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Paediatrics, Renmin Hospital, Wuhan University Wuhan 430060, Hubei Province, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
keywords: Atorvastatin; PI3K/AKT signaling pathway; TLR4/MYD88/NF-κB signaling pathway; apoptosis; leukemia