冬凌草甲素通过激活ERK途径诱导U937细胞凋亡  

Oridonin induced U937 cell apoptosis through ERK pathway

作　　者：刘艳秋[1] 游松[2] 田代真一[3] 小野寺敏 池岛乔[1] 

机构地区：[1]沈阳药科大学中日医药研究所,辽宁沈阳110016 [2]沈阳药科大学天然产物生物技术实验室,辽宁沈阳110016 [3]昭和药科大学病态科学教研室

出　　处：《中国中药杂志》2005年第23期1856-1859,共4页China Journal of Chinese Materia Medica

摘　　要：目的:研究冬凌草甲素诱导人组织淋巴瘤U937细胞凋亡的机制及ERK激酶在凋亡过程中的作用。方法:噻唑蓝(MTT)法,Hoechst 33258染色法,DNA凝胶电泳及Western blot检测法。结果:冬凌草甲素对U937细胞生长抑制作用呈时间剂量依赖性。27μmol.L-1冬凌草甲素作用细胞12 h后,Hoechst 33258染色细胞,出现明显凋亡小体,并诱导ERK发生磷酸化。ERK磷酸化抑制剂PD98059阻断了冬凌草甲素诱导的细胞生长抑制及DNA片段化。细胞内抑制凋亡蛋白Bcl-XL表达量时间依赖性减少,促凋亡蛋白Bax表达量增加,而ERK抑制剂可逆转这种作用。结论:冬凌草甲素(27μmol.L-1)诱导U937细胞凋亡,这种作用是通过活化ERK激酶,改变其下游Bax/Bcl-XL的表达比率,从而促进U937细胞发生凋亡。Objective： To study the mechanisms of ofidonin-induced U937 cell apoptosis, and to examine the role of ERK MAPK. Method： MTT, Hoechst 33258 staining, DNA agarose gel electrophoresis and Western blot analysis were used. Result： Oridonin inhibited U937 cell growth in a time- and dose-dependent manner. Apoptotic bodies were found with Hoechst 33258 staining after treatment with 27μmol·L^-1 oridonin. Simultaneously, ERK phosphorylation was significant. ERK inhibitor PD98059 partially blocked the growth-inhibitory effect as well as DNA fragmentation. The expression of antiapoptotic mitochondrial protein Bcl-XL decreased time-dependently, and that of proapoptotic protein Bax increased. However, PD98059 reversed the effect of oridonin on Bcl-XL and Bax. Conclusion： Oridonin induces U937 cell apoptosis through activation of ERK and alteration of the ratio of Bax/Bcl-XL

关 键 词：冬凌草甲素 U937细胞 凋亡 ERK激酶 

分 类 号：R285[医药卫生—中药学]