丹参酮ⅡA抗乳腺癌T47D细胞增殖的GPER途径研究  

Research on anti T47D breast cancer activity and its G protein-coupled estrogen receptor pathway of tanshinone ⅡA

作　　者：赵丕文[1] 臧金凤 陶仕英[1] 陈梦[1] 牛建昭[1] 

机构地区：[1]北京中医药大学基础医学院,北京100029

出　　处：《中国药理学通报》2015年第10期1458-1462,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81273887);高等学校创新引智计划(No B07007);北京中医药大学自主科研课题(No JYBZZ-JS014)

摘　　要：目的利用经典雌激素受体（estrogenic receptor,ER）和G蛋白偶联雌激素受体（G protein-coupled estrogen recep-tor,GPER）阳性乳腺癌T47D细胞,探索丹参酮IIA（TanshinoneIIA）对细胞增殖活性的影响及其GPER介导与调节功能.方法以GPER激动剂G1和GPER拮抗剂G15为工具药干预,并应用GPERSiRNA转染构建GPER基因沉默的T47D细胞,利用MTT细胞增殖实验观察丹参酮IIA对T47D细胞增殖速率的影响及GPER的介导作用.利用Westernblot方法检测丹参酮IIA对T47D细胞GPER表达情况的影响.结果1×10^-5 mol·L^-1 ～1×10^-7 mol·L^-1丹参酮IIA能够明显抑制T47D细胞增殖,且该抑制作用可被G1拮抗,可被G15增强.丹参酮IIA作用于GPER基因沉默的T47D细胞,该细胞表现出更为明显的生长抑制效应.West-ernblot测定结果表明,1×10^-5 mol·L^-1和1×10^-6 mol·L^-1丹参酮IIA可使T47D细胞GPER蛋白表达明显降低.结论丹参酮IIA具有抑制乳腺癌T47D细胞增殖的作用,该抑制作用可经GPER途径介导;且丹参酮IIA具有对靶细胞GPER表达的调节功能.Aim To explore the effects of tanshinone IIA on cell proliferation via G protein-coupled estrogen receptor inductive and regulative pathway in typical es-trogen receptor and G protein-coupled estrogen receptor positive T47D breast cancer cells. Methods The pro-liferation rate of T47 D cells influenced by tanshinone IIA was analyzed by MTT assay. G protein-coupled es-trogen receptor agonist G1 and GPER antagonist G15 were employed as tools. GPER SiRNA was applied to build GPER gene silence T47D cells. GPER expres-sion influenced by tanshinone IIA was measured by Western blot. Results The proliferation rates of T47D cells treated with 1 × 10 -5 mol·L-1 - 1 × 10 -7 mol· L-1 of tanshinone IIA were decreased significantly. Such effects could be attenuated by G1 or enhanced by G15 . Growth of GPER SiRNA transfected T47 D cells were significantly inhibited by 1 × 10 -5 mol·L-1 - 1 × 10 -7 mol·L-1 of tanshinone IIA treating. Result of Western blot showed that tanshinone IIA at 1 × 10 -5 mol· L-1 and 1 × 10 -6 mol · L-1 could induce de-crease of GPER protein expression in T47D cells. Conclusions Tanshinone IIA shows inhibitory effects on proliferation rate of T47 D breast cancer cells via GPER pathway. Tanshinone IIA could perform regula-tive function on GPER expression level in target cells.

关 键 词：丹参酮IIA 乳腺癌 T47D细胞 细胞增殖 G蛋白偶联雌激素受体 雌激素受体 基因沉默 

分 类 号：R284.1[医药卫生—中药学] R329.24[医药卫生—中医学]