中国中药杂志

2005, (23) 1856-1859

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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

刘艳秋;游松;田代真一;小野寺敏;池岛乔;
LIU Yan-qiu~(1,2),YOU Song~(2),TASHIRO Shin-ichi~(3),ONODERA Satoshi~(3),IKEJIMA Takashi~(1)(1.China-Japan Research Institute of Medical and Pharmaceutical Sciences,Shenyang Pharmaceutical University,Shenyang 110016,China;2.Laboratory of Natural Product Biotechnology,Shenyang Pharmaceutical University,Shenyang 110016,China;3.Department of Clinical and Biomedical Sciences,Showa Pharmaceutical University,Machida,Tokyo 194-8543,Japan)

摘要(Abstract):

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 oridonin-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 27 μmol·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-X_(L) decreased time-dependently,and that of proapoptotic protein Bax increased.However,PD98059 reversed the effect of oridonin on Bcl-X_(L) and Bax.Conclusion: Oridonin induces U937 cell apoptosis through activation of ERK and alteration of the ratio of Bax/Bcl-X_(L)

关键词(KeyWords): 冬凌草甲素;U937细胞;凋亡;ERK激酶
oridonin;U937 cells;apoptosis;ERK

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作者(Authors): 刘艳秋;游松;田代真一;小野寺敏;池岛乔;
LIU Yan-qiu~(1,2),YOU Song~(2),TASHIRO Shin-ichi~(3),ONODERA Satoshi~(3),IKEJIMA Takashi~(1)(1.China-Japan Research Institute of Medical and Pharmaceutical Sciences,Shenyang Pharmaceutical University,Shenyang 110016,China;2.Laboratory of Natural Product Biotechnology,Shenyang Pharmaceutical University,Shenyang 110016,China;3.Department of Clinical and Biomedical Sciences,Showa Pharmaceutical University,Machida,Tokyo 194-8543,Japan)

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