ABSTRACT
Objective: To investigate the molecular change of extracellular signal-regulated protein kinase (ERK) in Ras-MAPK signaling pathway after K 562 cells in nude mice were treated with simvastatin to elucidate whether ERK is involved in the regulation of simvastatin-induced apoptosis of K 562 cells. Methods: K 562 cells, the chronic myeloid leukemia (CML) cell line, were cultured in vitro and used to establish the K 562 xenografted model in BALB/c-nu/nu mice. The cell cycle of K 562 cells of control and two treatment groups was detected by flow cytometry (FCM). The advanced stage apoptotic change of K 562 cells induced by simvastatin was detected by TdT-mediated dUTP nick end labeling (TUNEL). The differential expressions of N-Ras and ERK 1 mRNA in Ras-MAPK signaling pathway were detected by RT-PCR. The changes of p-ERK protein were measured by immunohistochemical LDP method. Results: Simvastatin markedly inhibited the growth of xenografted K 562 tumor in nude mice. The volume and weight of tumors were significantly reduced with the increase in the dosage of simvastatin (P < 0.05, P < 0.01). Injection of 0.05 mg simvastatin per time induced significant G0/G1 arrest of K 562 cells in nude mice. Apoptosis of K 562 cells of nude mice could be induced by simvastatin at different dosages and the apoptotic rate was elevated by increasing the dosage of simvastatin (P < 0.01). The mRNA expressions of N-Ras and ERK 1 mRNA in K 562 cells were down-regulated by simvastatin at different dosages (P < 0.01). Compared with the control group, the p-ERK protein expression was down-regulated in 2 simvastatin-treated groups (P = 0.01, P < 0.01), respectively. Conclusion: Simvastatin depends on the Ras-MAPK signaling pathway. Downregulation of ERK mRNA and protein is involved in the induction of apoptosis of K 562 by simvastatin.