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汉黄芩素抑制胰岛素样生长因子-1对乳腺癌细胞增殖与雌激素受体α表达的促进作用和鸡胚尿囊膜的血管生成

马兴, 谢鲲鹏, 尚斐, 霍洪楠, 王丽梦, 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

本文旨在探讨汉黄芩素体外抗乳腺癌作用与胰岛素样生长因子-1 (insulin-like growth factor-1, IGF-1)通路和雌激素受体α (estrogen receptor α, ERα)的关系，及其对鸡胚尿囊膜血管生成的影响。用IGF-1、汉黄芩素或ERα抑制剂ICI182780单独或联合处理人乳腺癌MCF-7细胞，用MTT比色法检测细胞增殖情况，用Western blot方法检测ERα蛋白和p-Akt蛋白表达的变化；另外，采用孵育6日龄的鸡胚制备绒毛尿囊膜(chorioallantoic membrane, CAM)模型检测不同浓度汉黄芩素对新生血管抑制作用。结果显示，汉黄芩素和ICI182780均能显著抑制IGF-1的促细胞增殖作用。与IGF-1单独处理的细胞相比，汉黄芩素与IGF-1共同处理的细胞内ERα和p-Akt蛋白的表达水平显著降低；但与IGF-1和ICI182780共同处理的细胞相比无显著差异。另外，不同浓度的汉黄芩素对鸡胚CAM的血管生成均有显著的抑制作用。以上结果提示，汉黄芩素以ERα依赖方式抑制IGF-1介导的PI3K-Akt信号通路，抑制乳腺癌细胞增殖，并对鸡胚CAM新生血管的生成有明显的抑制作用。

关键词： 汉黄芩素; MCF-7乳腺癌细胞; 胰岛素样生长因子-1; 雌激素受体α

分类号：R7336

[Wogonin inhibits IGF-1-stimulated cell growth and estrogen receptor α expression in breast adenocarcinoma cell and angiogenesis of chick chorioallantoic membrane.] [Article in Chinese]

MA Xing, XIE Kun-Peng, SHANG Fei, HUO Hong-Nan, WANG Li-Meng, XIE Ming-Jie^*

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

Abstract

The aim of the present study was to investigate the involvements of insulin-like growth factor-1 (IGF-1) and estrogen receptor α (ERα) in the inhibitory effect of wogonin on the breast adenocarcinoma growth. Moreover, the effect of wogonin on the angiogenesis of chick chorioallantoic membrane (CAM) was also investigated. MCF-7 cells (human breast adenocarcinoma cell line) were subjected to several drugs, including IGF-1, wogonin and ER inhibitor ICI182780, alone or in combination. MTT assay was used to detect breast cancer proliferation. Western blot was used to analyze ERα and p-Akt expression levels. CAM models prepared from 6-day chicken eggs were employed to evaluate angiogenesis inhibition. The results showed wogonin and ICI182780 both exhibited a potent ability to blunt IGF-1-stimulated MCF-7 cell growth. Either of wogonin and ICI182780 significantly inhibited ERα and p-Akt expressions in IGF-1-treated cells. The inhibitory effect of wogonin showed no difference from that of ICI182780 on IGF-1-stimulated expressions of ERα and p-Akt. Meanwhile, wogonin at different concentrations showed significant inhibitory effect on CAM angiogenesis. These results suggest the inhibitory effect of wogonin on breast adenocarcinoma growth via inhibiting IGF-1-mediated PI3K-Akt pathway and regulating ERα expression. Furthermore, wogonin has a strong anti-angiogenic effect on CAM model.

Key words: wogonin; MCF-7 cell; insulin-like growth factor-1; estrogen receptor α

收稿日期：2011-09-15　　录用日期：2011-12-14

通讯作者：谢明杰　　E-mail: xmj1222@sina.com

引用本文：

马兴, 谢鲲鹏, 尚斐, 霍洪楠, 王丽梦, 谢明杰. 汉黄芩素抑制胰岛素样生长因子-1对乳腺癌细胞增殖与雌激素受体α表达的促进作用和鸡胚尿囊膜的血管生成[J]. 生理学报 2012; 64 (2): 207-212.

MA Xing, XIE Kun-Peng, SHANG Fei, HUO Hong-Nan, WANG Li-Meng, XIE Ming-Jie. [Wogonin inhibits IGF-1-stimulated cell growth and estrogen receptor α expression in breast adenocarcinoma cell and angiogenesis of chick chorioallantoic membrane.] [Article in Chinese]. Acta Physiol Sin 2012; 64 (2): 207-212 (in Chinese with English abstract).