机构：[1]National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China,[2]Breast Department, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China,广东省中医院[3]School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China,[4]Breast Department, Maternal and Child, Health Hospital of Sanya, Sanya, China,[5]Zhuhai Hospital of Guangdong Provincial Hospital Medicine, Zhuhai, China,[6]Warshel Institute for Computational Biology, The Chinese University of Hong Kong, Shenzhen, China,[7]School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, China,[8]School of Computer Science and Technology, University of Science and Technology of China, Hefei, China
Xihuang pill, an approved Chinese medicine formula (state medical permit number. Z11020073), is a commonly used adjuvant drug for cancer patients in China. Xihuang pill has a satisfactory effect in treating breast cancer in clinics, especially triple-negative breast cancer (TNBC), which is the most aggressive type of breast cancer, and finite effective therapies. However, the mechanism of Xihuang pill in treating TNBC remains unclear. The present study aims to explore the pharmacological mechanism of Xihuang pill in treating advanced TNBC. We identified the main chemical components of Xihuang pill by using HPLC-Q-TOF-MS/MS. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis shows that serum containing Xihuang pill (XS) had no obvious killing effect on any subtype of breast cancer cells, but it inhibited mammosphere colony formation of two TNBC cell lines (4T1 and HCC1806 cells) and could enhance the inhibitory effect of paclitaxel (PTX) on the proliferation of 4T1 and HCC1806 cells when combined with PTX. Seventy-six active compounds in Xihuang pill, their 300 protein targets, and 16667 TNBC stem cell-related genes were identified. The drug-herb-active compound-target gene-disease network and enrichment analyses were constructed with 190 overlapping candidate targets. Through text mining and molecular docking, the target gene NR3C2 and its active compound naringenin were selected for further validation. According to the TCGA database, we observed that a high expression of NR3C2 promoted a higher survival probability regarding overall survival (OS). In vitro experiments indicated that naringenin presented an identical effect to XS, possibly by regulating the NR3C2 expression. Overall, this study explored the effect of Xihuang pill in treating advanced TNBC cells and showed that naringenin, which is the key active compound of Xihuang pill, could lessen the stemness of TNBC cells to produce a synergistic effect on PTX by regulating the NR3C2 gene.
基金：
This study was supported by grants from the National Natural
Science Foundation of China (Nos. 81904206 and 81974571);
Guangdong Natural Science Foundation (No. 2017A030313719;
the Foundation Project of Guangzhou University of Traditional Chinese Medicine (No. XKP2019002); and Key project at central
government level: The ability establishment of sustainable use for
valuable Chinese medicine resources (No. 2060302). Hainan
health industry scientific research project(Nos 20A200121and
20A200525).
第一作者机构：[1]National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China,[2]Breast Department, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China,
共同第一作者：
通讯作者：
通讯机构：[6]Warshel Institute for Computational Biology, The Chinese University of Hong Kong, Shenzhen, China,[7]School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, China,
推荐引用方式(GB/T 7714)：
Yu-Zhu Zhang,Jia-Yao Yang,Rui-Xian Wu,et al.Network Pharmacology-Based Identification of Key Mechanisms of Xihuang Pill in the Treatment of Triple-Negative Breast Cancer Stem Cells[J].FRONTIERS IN PHARMACOLOGY.2021,12:doi:10.3389/fphar.2021.714628.
APA：
Yu-Zhu Zhang,Jia-Yao Yang,Rui-Xian Wu,Chen Fang,Hai Lu...&Qian-Jun Chen.(2021).Network Pharmacology-Based Identification of Key Mechanisms of Xihuang Pill in the Treatment of Triple-Negative Breast Cancer Stem Cells.FRONTIERS IN PHARMACOLOGY,12,
MLA：
Yu-Zhu Zhang,et al."Network Pharmacology-Based Identification of Key Mechanisms of Xihuang Pill in the Treatment of Triple-Negative Breast Cancer Stem Cells".FRONTIERS IN PHARMACOLOGY 12.(2021)
