冬凌草甲素通过ERK通路诱导U937细胞凋亡

[Oridonin induced U937 cell apoptosis through ERK pathway].

作者信息

Liu Yan-qiu, You Song, Tashiro Shin-ichi, Onodera Satoshi, Ikejima Takashi

机构信息

China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2005 Dec;30(23):1856-9.

PMID:16499027

Abstract

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 micromol x 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.

摘要

目的

研究冬凌草甲素诱导U937细胞凋亡的机制，并探讨细胞外信号调节激酶（ERK）丝裂原活化蛋白激酶（MAPK）的作用。

方法

采用MTT法、Hoechst 33258染色法、DNA琼脂糖凝胶电泳法及蛋白质免疫印迹分析。

结果

冬凌草甲素对U937细胞生长的抑制作用呈时间和剂量依赖性。用27 μmol·L⁻¹冬凌草甲素处理后，Hoechst 33258染色可见凋亡小体。同时，ERK磷酸化显著。ERK抑制剂PD98059部分阻断了生长抑制作用以及DNA片段化。抗凋亡线粒体蛋白Bcl-XL的表达呈时间依赖性降低，促凋亡蛋白Bax的表达增加。然而，PD98059逆转了冬凌草甲素对Bcl-XL和Bax的影响。