VP-16诱导HL-60细胞凋亡的研究  

APOTOSIS INDUCED BY ETOPOSIDE IN HL 60 CELLS

作　　者：何维敬[1] 张建业[2] 张庆殷[1] 张芬[3] 张莲英[2] 李登欣[2] 徐松德[2] 

机构地区：[1]山东医科大学附属医院检验科 [2]山东医科大学生物化学教研室 [3]山东医科大学第二附属医院外科

出　　处：《山东医科大学学报》2000年第1期13-16,共4页Acta Academiae Medicinae Shandong

基　　金：山东省科委资助课题

摘　　要：目的 :探讨 topo 抑制剂的抗瘤机制。方法 :选择人急性早幼粒细胞白血病细胞株 HL- 60为实验模型 ,以 VP- 1 6为诱导剂 ,用形态学观察、DNA电泳及流式细胞术 ( FCM)等方法对其凋亡情况进行了研究。 结果 :经 VP- 1 6处理的 HL- 60细胞呈典型凋亡形态学改变 ,出现梯状 DNA条带 ( DNA ladder) ,FCM DNA直方图上 G0 /G1峰前有明显的亚二倍体凋亡峰。表明经 VP- 1 6处理的 HL- 60细胞的确发生了凋亡 ,这种调亡作用对药物有浓度依赖性 ,但无严格时间依赖性 ,不需药物的持续作用 ,并与 S期细胞降低有关。而缺乏 topo 的 HPBL则无此作用 ,不受 VP- 1 6诱导而凋亡。结论 :诱导细胞凋亡是 VP- 1 6的抗瘤机制之一 ,且这种作用是由 topo 介导的。Objective: To explore the antitumor mechanism of topoisomerase Ⅱ inhibitors.Methods: Human acute promyelocytic cell line HL 60 cells were selected as target cells, etoposide as apoptosis inducer, and morphological observations, DNA gel electrophoresis and flow cytometic (FCM) methods were carried out to investigate apoptotic cells. Results: HL 60 cells incubated with different doses of VP 16(5 40mg/L) exhibited apoptotic morphological changes、typical“DNA ladder” lane in DNA gel electrophoresis and apparrent hypodiploid apoptotic peak(“sub G 1” peak) before “G 0/G 1” peak in FCM analysis, showing that the HL 60 cells are apoptotic. Futher investigation indicated that the apoptosis induced by VP 16 was drug dose dependent, but not apparently time dependent, and the increasing of apoptotic cells is paralleled with the decreasing of S phase cells. While HPBL cells which lacked topo Ⅱ cant be induced by VP 16 to apoptosis. Conclusion: Apoptosis induced by VP 16 is a primary mechanism in chemotherapy of leukemia and the action is mediated by topo Ⅱ.

关 键 词：HL-60细胞凋亡 鬼臼乙叉甙 抗肿瘤药 白血病 

分 类 号：R979.1[医药卫生—药品] R733.705[医药卫生—药学]