胆固醇合成抑制剂辛伐他汀对K562细胞增殖和凋亡的作用  

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

作　　者：任汉云[1] 张念先[1] 徐红[1] 陆道培[1] 

机构地区：[1]北京大学人民医院,北京大学血液病研究所,100044

出　　处：《中华血液学杂志》2001年第2期72-75,共4页Chinese Journal of Hematology

基　　金：国家自然科学基金!资助项目 (39770 833)

摘　　要：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K5 6 2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K5 6 2细胞增殖及凋亡的作用 ,以及该制剂联合化疗药物对K5 6 2细胞凋亡的影响。结果　辛伐他汀明显抑制K5 6 2细胞增殖并诱导其凋亡 ,并能增强K5 6 2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K5 6 2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。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.

关 键 词：慢性髓细胞白血病 药物疗法 细胞增殖 细胞凋亡 辛伐他汀 

分 类 号：R733.72[医药卫生—肿瘤] R979.1[医药卫生—临床医学]