Literature DB >> 26064227

Study on the function and mechanism of atorvastatin in regulating leukemic cell apoptosis by the PI3K/Akt pathway.

Miao Liu1, Rong Tang1, Yi Jiang1.   

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.

Entities:  

Keywords:  Atorvastatin; PI3K/AKT signaling pathway; TLR4/MYD88/NF-κB signaling pathway; apoptosis; leukemia

Year:  2015        PMID: 26064227      PMCID: PMC4443061     

Source DB:  PubMed          Journal:  Int J Clin Exp Med        ISSN: 1940-5901


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