雌激素受体-α36参与淫羊藿素诱导的三阴性乳腺癌细胞生长抑制。

Estrogen receptor-α36 is involved in icaritin induced growth inhibition of triple-negative breast cancer cells.

作者信息

Wang Xue, Zheng Nan, Dong Jing, Wang Xuming, Liu Lijiang, Huang Jian

机构信息

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei Province 430072, PR China.

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei Province 430072, PR China; College of Bioengineering, Wuhan Polytechnic, Wuhan, Hubei Province 430074, PR China.

出版信息

J Steroid Biochem Mol Biol. 2017 Jul;171:318-327. doi: 10.1016/j.jsbmb.2017.05.009. Epub 2017 May 18.

DOI:10.1016/j.jsbmb.2017.05.009

Abstract

A sub-class of ER-negative breast cancer that is negative for ER, PR and HER2 expression known as triple-negative breast cancer (TNBC) is highly malignant and lacks effective treatment. Recently, it has been reported that an isoform of estrogen receptor-alpha ER-α36 is expressed and plays a critical role in development of TNBC. ER-α36 forms a positive regulatory loop with epidermal growth factor receptor (EGFR), which promotes malignant growth of TNBC cells. Thus, ER-α36 has been proposed as an important target for development of novel drugs for TNBC. In this study, we evaluated the effects of icaritin, a prenylflavonoid derivant purified from Epimedium Genus, on growth of TNBC cells and examined the possible underlying mechanisms. Our study demonstrated that icartin decreased both ER-α36 and EGFR protein expression, and induced apoptosis in TNBC MDA-MB-231 and MDA-MB-453 cells. We also found that icaritin inhibited ER-α36-mediated MAPK/ERK pathway and cyclin D1 induction by estrogen. Our results thus indicated that icaritin has a potential to be developed into a novel therapeutic agent for human TNBC.

摘要

雌激素受体（ER）阴性、孕激素受体（PR）阴性且人表皮生长因子受体2（HER2）表达阴性的乳腺癌亚类，即三阴性乳腺癌（TNBC），具有高度侵袭性且缺乏有效的治疗方法。最近，有报道称雌激素受体α的一种亚型ER-α36表达，并在TNBC的发展中起关键作用。ER-α36与表皮生长因子受体（EGFR）形成正调控环，促进TNBC细胞的恶性生长。因此，ER-α36被认为是开发TNBC新型药物的重要靶点。在本研究中，我们评估了从淫羊藿属植物中纯化得到的异戊烯基黄酮衍生物淫羊藿素对TNBC细胞生长的影响，并探讨了其潜在机制。我们的研究表明，淫羊藿素可降低ER-α36和EGFR蛋白表达，并诱导TNBC的MDA-MB-231和MDA-MB-453细胞凋亡。我们还发现，淫羊藿素可抑制ER-α36介导的丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）通路以及雌激素诱导的细胞周期蛋白D1表达。因此，我们的结果表明，淫羊藿素具有开发成为治疗人类TNBC新型药物的潜力。