鼠尾草酚抗乳腺癌细胞增殖活性及其雌激素受体亚型介导和调节机制的研究  

Effect of carnosol against proliferative activity of breast cancer cells and its estrogen receptor subtype's mediation and regulation mechanisms

作　　者：赵丕文[1,2] David Yue-Wei LEE Zhongze Ma 孙艳玲[1] 陶仕英[1] 臧金凤 牛建昭[1] 

机构地区：[1]北京中医药大学基础医学院,北京100029 [2]Mclean Hospital,Harvard Medical School,belmontma02478

出　　处：《中国中药杂志》2014年第17期3344-3348,共5页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81273887);高等学校创新引智计划(B07007);北京中医药大学自主科研课题(JYBZZ-JS014)

摘　　要：既往研究已经表明,鼠尾草酚(carnoso1)具有一定的抗乳腺癌效应,但其ER亚型特异性调节和介导机制与该物质抑制细胞增殖效应的相关性尚不清楚。该研究利用雌激素受体(ER)阳性乳腺癌T47D细胞观察鼠尾草酚对细胞增殖活性的影响及其雌激素受体α,卢亚型特异性介导和调节机制。以ERα和ERβ特异性拮抗剂MPP,PHTPP为工具药,采用MTT细胞增殖实验观察鼠尾草酚对T47D细胞增殖的影响;检测T47D细胞增殖周期的变化。利用Western blot方法检测鼠尾草酚对T47D细胞ERα和ERβ表达情况的影响。研究发现,1×10^(-5)~1×10^(-7)mol·L^(-1)鼠尾草酚能够显著抑制T47D细胞增殖,该抑制作用可被ERα拮抗剂MPP增强、被ERβ拮抗剂PHTPP减弱;1×10^(-1),1×10^(-6)mol·L^(-1)鼠尾草酚可使T47D细胞增殖指数显著下降。Western blot检测结果显示1×10^(-5),1×10^(-6)mol·L^(-1)鼠尾草酚可使T47D细胞ERα和ERβ蛋白表达显著增加,并可明显提高ERα/ERβ。结果表明鼠尾草酚具有抑制ER阳性乳腺癌细胞增殖的作用,其效应是通过靶细胞雌激素受体,特别是ERβ途径实现的;同时,鼠尾草酚对靶细胞雌激素受体ERα和ERβ亚型的表达及其比例具有调节功能。Carnosol has been proved to have anti-breast cancer effect in previous research. But its ER subtype＇s specific regulation and mediation mechanisms remain unclear. The aim of this study is to observe the effect of carnosol on cell proliferation and its estrogen receptor α and β＇s specific regulation and mediation mechanisms with ER positive breast cancer T47D cell. With estrogen receptor α and β antagonists MPP and PHTPP as tools, the MTT cell proliferation assay was performed to observe the effect of carnosol on T47D cell proliferation. The changes in the T47D cell proliferation cycle were detected by flow cytometry. The effect of carnosol on ERα and ERβ expressions of T47D cells was measured by Western blot. The findings showed that 1 × 10-5-1 × 10-Tmol · L^-1 carnosol could significantly inhibit the T47D cell proliferation, which could be enhanced by MPP or weakened by PHTPP. Meanwhile, 1 × 10 -5 mol · L-5or 1 × 10-6 mol · L-1 carnosol could significantly increase ERa and ERfl expressions of T47D cells, and remarkably increase ERa/ERfl ratio. The results showed that carnosol showed the inhibitory effect on the proliferation of ER positive breast cancer cells through target cell ER, especially ERfl pathway. In the meantime, carnosol could regulate expressions and proportions of target cell ER subtype ERa and ER/3.

关 键 词：鼠尾草酚 乳腺癌 T47D细胞 细胞增殖 细胞周期 雌激素受体 

分 类 号：R285.5[医药卫生—中药学]