The Effects Of Atorvastatin On The Proliferation Of K562Cells And Its Mechanisms

Objective:1.To observe the effects of atorvastatin on the cell proliferation and apoptosis ofK562cells.2.To explore the anti-proliferative mechanism of atorvastatin in K562cells.Methods:1.The human CML K562cell line was incubated conventionally, and the cellsin logarithmic growth phase were used to perform study.2. CCK-8assay was employed to evaluate the effects of atorvastatin on theproliferative inhibition of K562cells after treated by various concentrations ofatorvastatin for24h,48h,72h.3.The apoptosis of K562cells incubated with various concentrations ofatorvastatin for72h by AnnexinV-FITC/PI staining.4. Flow cytometry was used to detect the cell cycle of K562cells treated withvarious concentrations of atorvastatin for72h.5. The activities of caspase-3,-8,-9of K562cells were incubated with variousconcentrations of atorvastatin for72h by colorimetric method.6. qRT-PCR was employed to analyze the mRNA expression levels of Bcl-2andPDCD5in K562cells treated with various concentrations of atorvastatin for72h.Results:1.Atorvastatin could inhibit growth and proliferation of K562cells in a time-and dose-dependent manner（P<0.05）.2.12.5μmol/L,25μmol/L and50μmol/L atorvastatin could markedly induceapoptosis of K562cells after treatment for72h with the apoptotic rate of (14.11±1.12)%、(22.89±0.87)%and (47.35±1.41)%respectively, compared with thecontrol group of（4.85±0.91）%（P<0.01）. There were also significant differencesamong the three atorvastatin-treated k562cells groups(P<0.01).3.After the treatment of12.5μmol/L,25μmol/L and50μmol/L atorvastatin onk562cells for72h, the percentage of G0/G1phase cells increased accompanying cell cycle arrest in G1/S compared with the control group（P<0.01）, while thepercentage of S phase cells decreased, Significant differences were observed amongthe three atorvastatin-treated k562cells groups(p<0.01).4.The caspase-3,-8,-9activities of K562cells treated with12.5μmol/L,25μmol/L and50μmol/L atorvastatin elevated markedly when compared with thecontrol group （P<0.01）. Statistical difference were found among the threeatorvastatin-treated k562cells groups(P<0.01).5. qRT-PCR examination indicated that25μmol/L and50μmol/L atorvastatincould downregulate Bcl-2mRNA levels and upregulate PDCD5mRNA levelssignificantly when compared with the control group（P<0.01）.Conclusions:1. Atorvastatin has been found to inhibit proliferation of K562cells significantlyin a time-and dose-dependent fashion.2. Atorvastatin has the potent to induce apoptosis of K562cells and arrest cellcycle in G1/S phase.3. The underlying mechanism whereby atorvastatin induced apoptosis of K562cells might be associated with activation of the caspase cascade includingcaspase-8,-9and caspase-3.4. The proapoptotic mechanisms of atorvastatin in K562cells could be partlyascribed to inhibiting the mRNA expression of Bcl-2and increasing the mRNAexpression of PDCD5significantly.