Simvastatin-induced Apoptosis of Human Leukemia K562 Cells:An Experimental Study

OBJECTIVE:To study the simvastatin-induced apoptosis of K562 cells and its mechanism. METHODS: 72 hours after exposure to 0 (control),10,20,30 μmol·L-1 simvastatin,the apoptotic rate of cells was measured with annexinⅤ-FITC/PI double staining method. Apoptotic ladder bands were detected by DNA Ladder experiment. Plasmosin,microsomal proteins and mitochondrial proteins were isolated by mitochondria isolation kit. The mRNA expression levels of RP78,caspase-9,caspase-3,and GADD153 were determined by RT-PCR. The protein expression levels of GRP78,caspase-12,caspase-9,and caspase-3,GADD153 and cytochrome C were determined by western blot method. RESULTS: Compared to control group,72 hours after exposure to 10,20,and 30 μmol·L-1 simvastatin,typical apoptotic bands were observed,and the apoptotic rates of K562 cells were 12.41%,19.08%,and 23.41% (P0.01),respectively. The mRNA expression levels of GRP78,caspase-9,caspase-3 and GADD153 were up-regulated (P0.05) but the protein expression levels of caspase-12,caspase-9 and caspase-3 were down-regulated. Caspase-12 localized in the endoplasmic reticulum,cytochrome C was released from mitochondria;the proteins levels of GRP78 and GADD153 were up-regulated. CONCLUSION: Simvastatin may induce apoptosis of K562 cells though endoplasmic reticulum and mitochondria pathways.