Simvastatin Induced K562 Cells To Apoptosis By Death Receptor Signal Pathway And Its Mechanism

Objective: To investigate the effects of simvastatin on the cell proliferation and apoptosis of K562 cells, and deeply investigate the effect of simvastatin on death receptor signal pathway in K562 cells.Methods: 1. K562 cells had been treated with 20μmol/L simvastatin for different tim(e24h,48h,72h) for following experiments: 1. MTT assay was employed to evaluate the effects of simvastatin on the proliferative inhibition of K562 cells. 2. Cell cycle of K562 cells treated with simvastatin was assayed by flow cytometry. AnnexinⅤ-FITC/PI staining was performed to confirm the apoptosis of K562 cells incubated with simvastatin for different time. 3. RT-PCR was used to detect the mRNA expression of FADD,TRADD and DR5 in death receptor signal pathway.The total protein was extracted and the changes of FADD,TRADD and DR5 proteins were checked by western blot.Results: 1. Simvastatin could inhibit proliferation of K562 cells in a time and concentration dependent manner. 2. The percentage of G0/G1 phase cells increased while the percentage of S phase cells decreased since K562 cells had been treated with simvastatin for 24h, arrestting cell cycle in G1/S phase. The apoptosis rate increased following the treated time of simvastatin. K562 cells could be induced to undergo apoptosis after 20μmol/L simvastatin treatment for 24h,48h and 72h,the apoptotic rate was(9.41±0.86)%,(12.41±0.35)% and(19.08±1.05)% respectively. Compared with the control group, it was significantly higher(P<0.01). 3. There is visible difference between treated groups and control groups in mRNA level of FADD,TRADD and DR5(P<0.01 respectively). The contents of proteins in treated groups were obviously different from the control groups in western blot results, and also increased with the treated time.Conclusions: 1. Simvastatin can inhibit proliferation of K562 cells and induce them to undergo apoptosis in a time and concentration dependent manner. 2. With the effect of sivastatin in death receptor signal pathway, the mRNA level and protein level of key genes in death receptor signal pathway had evident changes which show that simvastatin could induce the apoptosis of k562 cells, and the death receptor signal pathway maybe participates in. 3.Our research explores the anti-leukemia mechanisms of simvastatin systematically, which might be useful for clinical therapy and treatment of chronic myelocytic leukemia.