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秦皮素体外抗乳腺癌作用与雌激素信号通路的关系

霍洪楠, 谢鲲鹏, 王丽梦, 姜英, 邹伟, 谢明杰^*

辽宁师范大学生命科学学院，辽宁省生物技术与分子药物研发重点实验室，大连 116081

摘要

雌激素信号通路在调节乳腺癌细胞增殖和凋亡等生理机能中发挥重要功能。本文采用MTT法、流式细胞分析、Western blot 等方法，通过检测秦皮素对MCF-7细胞周期分布、凋亡、雌激素受体蛋白、靶基因蛋白cyclin D1和Bcl-2、MAPK和PI3K信号通路等的影响，来探讨秦皮素的抗乳腺癌作用机制。实验结果显示，秦皮素对E2β促MCF-7细胞增殖具有明显的抑制作用，呈时间和剂量依赖性。秦皮素可抑制E2β的抗细胞凋亡作用，将细胞周期阻滞在G0/G1期。同时，秦皮素还能降低MCF-7细胞中ERα蛋白的表达，通过下调靶基因蛋白cyclin D1和Bcl-2来影响E2β介导的基因组信号通路；通过抑制MAPK/Erk1/2蛋白的表达影响E2β介导的非基因组信号通路。研究结果表明，秦皮素可通过影响E2β介导的基因组途径和非基因组途径发挥抗乳腺癌作用。

关键词： 秦皮素; MCF-7细胞; MAPK/Erk1/2

分类号：R736.3

[Relationship between the inhibitory effect of fraxetin on breast cancer and estrogen signaling pathway.] [Article in Chinese]

HUO Hong-Nan, XIE Kun-Peng, WANG Li-Meng, JIANG Ying, ZOU Wei, XIE Ming-Jie^*

College of Life Science, Liaoning Normal University, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Dalian 116081, China

Abstract

Estrogen signaling pathways play an important role in the regulation of the physiological function of breast cancer cell proliferation and apoptosis. The article used MTT assay, flow cytometer analysis and Western blot to detect the inhibition of fraxetin on MCF-7 cell cycle distribution and apoptosis, ERα, cyclin D1 and Bcl-2 expression levels, MAPK and PI3K signaling pathway to investigate the mechanism of anti-breast cancer of fraxetin. The results showed fraxetin inhibited E2β-stimulated MCF-7 cell proliferation in a dose- and time-dependent manner, reversed E2β-induced anti-apoptosis and promoted G₀/G₁ phase arrest. After treatment with fraxetin, the expression of ERα in MCF-7 cell was decreased, and estrogen genomic signaling pathway was inhibited by down-regulating the expression of cyclin D1 and Bcl-2 proteins. After MCF-7 cells were treated with fraxetin, the expressions of MAPK/Erk1/2 protein were reduced, which affected estrogen non-genomic signaling pathway. The results suggest fraxetin plays a part in anti-breast cancer function through E2β-mediated genomic and non-genomic signaling pathways.

Key words: fraxetin; MCF-7 cell; MAPK/Erk1/2

收稿日期：2012-11-06　　录用日期：2013-01-21

通讯作者：谢明杰　　E-mail: xmj1222@sina.com

引用本文：

霍洪楠, 谢鲲鹏, 王丽梦, 姜英, 邹伟, 谢明杰. 秦皮素体外抗乳腺癌作用与雌激素信号通路的关系[J]. 生理学报 2013; 65 (3): 323-328.

HUO Hong-Nan, XIE Kun-Peng, WANG Li-Meng, JIANG Ying, ZOU Wei, XIE Ming-Jie. [Relationship between the inhibitory effect of fraxetin on breast cancer and estrogen signaling pathway.] [Article in Chinese]. Acta Physiol Sin 2013; 65 (3): 323-328 (in Chinese with English abstract).