Antiestrogenic Activity of the Xi-Huang Formula for Breast Cancer by Targeting the Estrogen Receptor α

作者：Jian Hao, Ziqi Jin, Hongxu Zhu, Xiaohui Liu, Yu Mao, Xue Yang, Li Gao, Dan Liu, Dan Chen, Xiong-Zhi Wu · 发表于：Cellular Physiology and Biochemistry · 年份：2018 · DOI：10.1159/000491533 · 被引用次数：18 · 研究领域：Estrogen and related hormone effects、Pharmacological Effects of Medicinal Plants、Flavonoids in Medical Research

BACKGROUND/AIMS: The Xi-Huang (XH) formula has been used for breast cancer treatment in traditional Chinese medicine (TCM) since 1740. In this study, we show that, XH extract could suppress the growth of breast cancer cells in vitro and in vivo, and that it preferentially inhibits cell growth of estrogen receptor positive (ER+) breast cancer cells. Presently, little is known about the potential mechanism of XH and our studies aim to elucidate its mechanism in breast cancer treatment. METHODS: Network-based systems biology and molecular docking analyses were performed to predict explicit targets of XH and active ingredients in XH. The effects of XH on cell viability, cell cycle, apoptosis in different breast cancer cell lines were analyzed in vitro. A model of transplanted tumors on nude mice was used to study the anticancer effect in vivo. Various techniques, including western blotting, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, co-immunoprecipitation and immunohistochemical were utilized to assess the expression of targets of XH in vitro and in vivo. RNA sequencing (RNA-seq) was performed to study the gene targets of XH. Furthermore, we analyzed of protein-ligand binding reactions by isothermal titration calorimetry (ITC). RESULTS: Using network-based systems biology and molecular docking analyses, we predicted that the major targets of XH were ERα and HSP90. Moreover, we found that, XH mediated its anti-cancer effects by promoting the disa...