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木犀草素下调AEG-1和MMP-2的表达对血管生成和乳腺癌细胞侵袭性的抑制作用

姜英, 谢鲲鹏, 霍洪楠, 王丽梦, 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

本研究探讨木犀草素对乳腺癌细胞增殖及其对血管生成和乳腺癌细胞侵袭性作用的影响。采用MTT比色法检测木犀草素对乳腺癌细胞增殖的作用；鸡胚绒毛尿囊膜(chick chorioallantoic membrane, CAM)模型检测木犀草素对新生血管生成的影响；细胞划痕法检测木犀草素对乳腺癌细胞侵袭性的情况；Western blot方法检测凋亡抑制基因Bcl-2蛋白、星形胶质细胞升高基因-1 (astrocyte elevated gene-1, AEG-1)蛋白、基质金属蛋白酶-2 (matrix metalloproteinase-2, MMP-2)蛋白的表达。实验结果显示，木犀草素以时间和剂量依赖的方式抑制MCF-7细胞增殖，下调Bcl-2蛋白表达；木犀草素能显著抑制CAM中新生血管生成；与对照组相比，60 μmol/L木犀草素作用MCF-7细胞48 h后，其迁移率降低了71.07 % (P < 0.01)，AEG-1和MMP-2蛋白表达量分别下降了82.34%和85.70% (P < 0.05)。以上结果表明，木犀草素能有效地抑制乳腺癌MCF-7细胞增殖，抑制抑癌基因Bcl-2蛋白表达，抑制血管新生和乳腺癌细胞的侵袭，下调AEG-1和MMP-2表达。

关键词： 木犀草素; 基质金属蛋白酶-2; 人乳腺癌细胞株MCF-7; 鸡胚绒毛尿囊膜

分类号：R7337

[Inhibitory effect of luteolin on the angiogenesis of chick chorioallantoic membrane and invasion of breast cancer cells via downregulation of AEG-1 and MMP-2] [Article in Chinese]

JIANG Ying, XIE Kun-Peng, HUO Hong-Nan, WANG Li-Meng, , 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

The purpose of the present study was to investigate the effect of luteolin on the angiogenesis and invasion of breast cancer cells. MTT assay was used to examine breast cancer proliferation. The chick chorioallantoic membrane model was used to assess the angiogenesis effect. Wound healing assay was used to assess cell invasion ability. Western blot was used to analyze Bcl-2, AEG-1 and MMP-2 expression levels. The results showed luteolin inhibited MCF-7 cells proliferation in a dose- and time-dependent manner, and the expression of Bcl-2 protein was decreased. Luteolin had a strong anti-angiogenesis of chick chorioallantoic membrane. After treatment of MCF-7 cells with luteolin at 60 μmol/L for 48 h, migration rate was reduced by 71.07% compared with control (P < 0.01). After treatment of MCF-7 cells with luteolin at 60 μmol/L for 48 h, the expression of AEG-1 and MMP-2 was reduced by 82.34% (P < 0.05) and 85.70% (P < 0.05) respectively, compared with control. In conclusion, the results suggest that luteolin can inhibit the proliferation of breast cancer cells, and suppress the expression of Bcl-2. Furthermore, luteolin has strong anti-angiogenesis of chick chorioallantoic membrane and anti-invasive activity on breast cancer cells, and down-regulates the expression of AEG-1 and MMP-2.

Key words: luteolin; MMP-2; MCF-7; chick chorioallantoic membrane

收稿日期：2013-05-22　　录用日期：2013-07-24

通讯作者：谢明杰　　E-mail: xmj1222@sina.com

引用本文：

姜英, 谢鲲鹏, 霍洪楠, 王丽梦, 邹伟, 谢明杰. 木犀草素下调AEG-1和MMP-2的表达对血管生成和乳腺癌细胞侵袭性的抑制作用[J]. 生理学报 2013; 65 (5): 513-518.

JIANG Ying, XIE Kun-Peng, HUO Hong-Nan, WANG Li-Meng, , ZOU Wei, XIE Ming-Jie. [Inhibitory effect of luteolin on the angiogenesis of chick chorioallantoic membrane and invasion of breast cancer cells via downregulation of AEG-1 and MMP-2] [Article in Chinese]. Acta Physiol Sin 2013; 65 (5): 513-518 (in Chinese with English abstract).