SYUNZ-4诱导U937细胞凋亡及机制研究  

The mechanism for SYUNZ-4 inducing apoptosis of U937 cells

作　　者：王一[1,3] 谢冰芬[1] 朱孝峰[1] 冯公侃[1] 邓蓉[1] 刘健楠[1] 郭经峰[1] 吴海强[2] 古练权[2] 姜文奇[1] 刘宗潮[1] 

机构地区：[1]华南肿瘤学国家重点实验室,中山大学肿瘤防治中心 [2]中山大学药学院 [3]陕西省人民医院血液科,710068

出　　处：《中华血液学杂志》2006年第11期762-765,共4页Chinese Journal of Hematology

基　　金：国家自然科学基金资助项目(20272085和30271601);广东省自然科学基金博士启动基金资助项目(530803)

摘　　要：目的探讨半合成紫草萘醌化合物SYUNZ-4对U937细胞的诱导凋亡作用及机制。方法锥虫蓝拒染实验和MTT法分析SYUNZ-4对U937细胞的生长抑制作用;DNA电泳、荧光显微镜观察细胞形态及流式细胞术检测细胞凋亡;Western blot法分析凋亡相关蛋白表达的变化。结果SYUNZ-4抑制U937细胞生长并呈时间和浓度依赖性,48 h的半数抑制浓度(IC50)为3．62μg／ml;经SYUNZ-4处理的U937细胞可见DNA梯形条带、细胞核浓缩和凋亡小体;6μg／ml SYUNZ-4处理U937细胞6,12,24 h,细胞凋亡率分别为(12．2±6．5)％、(25．3±11．4)％和(56．2±6．5)％,对照组凋亡率为(2．1±0．8)％(P<0．05);SYUNZ-4可活化U937细胞中的caspase-3、caspase-8、caspase-9和PARP,上调Bax、P21、P27、Fas和FasL的表达,下调Bcl-xL水平,对Bcl-2、BID和P53表达无影响。结论SYUNZ-4在体外可诱导U937细胞凋亡。caspase家族蛋白及其相关信号分子参与了凋亡的调节。Objective To investigate apoptotic effect of SYUNZ-4 on U937 cells , and its molecular mechanism. Methods Cell proliferation and viability were detected by MTT trypan blue exclusion assay. DNA electrophoresis, fluorescence microscopy and FACS were used to detect apoptosis. Apoptosis related proteins were analyzed by Western blot. Results The inhibition of cell proliferation in U937 cells exposed to SYUNZ-4 was dose- and time- dependent. SYUNZ-4 induced DNA ladder, nuclear condensation and apoptotic bodies and significantly increased apoptosis in U937 ceils when exposed a dose of 6 μg/ml for 6, 12 and 24 h, the apoptotic cells were（ 12.2 ± 6.5 ） %, （ 25.3 ± 11.4 ） %, and （ 25.3 ± 11.4 ） %, respectively, which was markedly higher than that of control [ （2. 1 ± 0.8 ） % ] （ P 〈 0.05 ）. SYUNZ-4 activated caspase-3, caspase-8, caspase-9 and PARP, up-regulated proteins level of Fas, FasL, Bax, P21 and P27, down-regulated expression of Bcl-xL, while had no effect on gene of Bcl-2 and BID. Conclusion Shikonin derivative- SYUNZ-4 can induce U937 leukemic cell apoptosis in vitro through activation of caspase family and related signal molecules.

关 键 词：紫草 U937细胞 细胞凋亡 

分 类 号：R285[医药卫生—中药学]