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

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

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 receptorα,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。

The aim of the present study was to investigate the involvements of insulin-like growth factor-1 （IGF-1） and estrogen re-ceptor α （ERα） in the inhibitory effect of wogonin on the breast adenocarcinoma growth.Moreover,the effect of wogonin on the an-giogenesis 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-stimulat-ed expressions of ERα and p-Akt.Meanwhile,wogonin at different concentrations showed significant inhibitory effect on CAM an-giogenesis.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.