胆固醇合成抑制剂辛伐他汀对K562细胞增殖和凋亡的作用

目的 探讨慢性髓细胞白血病（CML）细胞抗凋亡机制和诱导CML细胞凋亡的有效方法。方法 采用CML细胞株K562体外培养、用^3H-TdR掺入法及DNA末端标记法观察胆固醇合成限速酶3－羟－3－甲基戊二酰辅酶A（HMG－CoA)还原酶抑制剂辛伐他汀对K562细胞增殖及凋亡的作用，以及该制剂联合化疗药物对K562细胞凋亡的影响。结果 辛伐他汀明显抑制562细胞增殖并诱导其凋亡，并能增强K562细胞对化疗药物的敏感性。加入HMG－CoA下游产物甲羟戊酸可完全逆转这种作用。结论 辛伐他汀通过抑制甲羟戊酸代谢途径抑制K562细胞增殖并诱导其凋亡，表明HMG－CoA还原酶抑制剂作为治疗CML的药物具有潜在的应用价值。

Inhibition of proliferation and induction of apoptosis by simvastatin in K562 le ukemic cell line

Objective To investigate the anti apoptotic mechanism and explore approach to inhibiting proliferation and inducing apoptosis of chronic myclogenous leukemia (CML) cells. Methods K562 cell line was used to evaluate the effects of simvastatin, an inhibitor of 3 hydroxy 3 methylglutaryl coenzyme A (HMG CoA) reductase, and the combination of simvastatin with chemotherapeutic agents on the proliferation and apoptosis of CML cells. Results Simvastatin could significantly inhibit proliferation and induce apoptosis of K562 cells,and could increase the sensitivity of K562 cells to chemotherapeutic agents. Addition of mevalonate, the immediate product of HMG CoA, could completely reverse this effect. Conclusion Simvastatin inhibited proliferation and induced apoptosis of K562 cells through inhibiting the metabolic pathway of mevalonate. It is promising that HMG CoA reductase inhibitors may be an effective chemotherapeutic approach to the treatment of CML.