机构：[a]Integrative Research Laboratory of Breast Cancer, Discipline of Integrated Chinese and Western Medicine, the Research Center of Integrative Medicine, School of Basic Medical Sciences & the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China广东省中医院[b]Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China广东省中医院[c]Post-doctoral Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China[d]School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China[e]School of Pharmacy, Guangdong Pharmaceutical University, China
Background: Breast cancer remains the most common female malignancy and metastasis is the leading cause of death in breast cancer patients. Oldenlandia diffusa has been empirically and extensively used as an adjuvant therapy for metastatic breast cancer patients in Traditional Chinese Medicine (TCM) with proven efficacy. However, its anti-metastasis mechanism has been poorly revealed. Methods: Multiple molecular biology experiments as well as network pharmacology, bioinformatics analysis were conducted to investigate the anti-metastasis mechanism of Oldenlandia diffusa in breast cancer. Results: We demonstrated that ethanol extract of Oldenlandia diffusa (EEOD) significantly inhibited proliferation and induced apoptosis of high-metastatic breast cancer cell lines MDA-MB-231 and MDA-MB-453, while having no obvious cytotoxic effect on multiple nonmalignant cells. Furthermore, EEOD remarkably suppressed the migration and invasion capacities of the above breast cancer cells by modulating the matrix metalloproteinases (MMPs) and the epithelial-mesenchymal transition (EMT) pathway. More importantly, EEOD also significantly inhibited breast cancer metastasis in zebrafish xenotransplantation model in vivo. Network pharmacology and bioinformatics analysis further demonstrated that EEOD yielded 12 candidate compounds and 225 potential targets, and shared 85 putative targets associated with breast cancer metastasis. Mechanistically, RNA sequencing and experimental validation results suggested that EEOD might inhibit breast cancer metastasis by attenuating the expression of caveolin-1 (Cav-1) as overexpression of Cav-1 could weaken the anti-metastasis efficacy of EEOD. Conclusions: Overall, our findings proved that EEOD could inhibit breast cancer metastasis by attenuating the expression of Cav-1, highlighting the use of EEOD as an adjunctive therapy for metastatic breast cancer patients. This study also provides novel insights into network pharmacology and bioinformatics analysis as effective tools to illuminate the scientific basis of TCM.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81703749, 81873306, 81573651, 81703764]; Guangdong Science and Technology Department [2016A030306025]; Guangzhou Science, Technology and Innovation Commission [805296345055]; Pearl River S&T Nova Program of Guangzhou [201506010098]; Guangdong Provincial Science and Technology Agency [2014A020221047]; Guangdong Provincial Academy of Traditional Chinese Medicine [2014A020221047]; Guangdong High-level University Construction Project [A1-AFD018161Z1510, A1-AFD018171Z11102, A1-AFD018171Z11101]; Guangdong High-level Personnel of Special Support Program [A1-3002-16-111-003]; Guangdong traditional Chinese medicine bureau [20181132, 20182044]; Postdoctoral Science Foundation of ChinaChina Postdoctoral Science Foundation [2017M612644, 2018T110861, 2017M622669]; Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [2017A030310213]; Guangdong provincial key project [2016kzdxm032]; Science and Technology Planning Project of Guangdong Province [2017B030314166]; Specific Research Fund for TCM Science and Technology of Guangdong provincial Hospital of Chinese Medicine [YN2018MJ07, YN2018QJ08]
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|3 区医学
小类|3 区医学：研究与实验3 区药学
最新[2025]版：
大类|2 区医学
小类|2 区医学：研究与实验2 区药学
JCR分区：
出版当年[2017]版：
Q2PHARMACOLOGY & PHARMACYQ2MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q1MEDICINE, RESEARCH & EXPERIMENTALQ1PHARMACOLOGY & PHARMACY
第一作者机构：[a]Integrative Research Laboratory of Breast Cancer, Discipline of Integrated Chinese and Western Medicine, the Research Center of Integrative Medicine, School of Basic Medical Sciences & the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China[b]Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China
共同第一作者：
通讯作者：
通讯机构：[a]Integrative Research Laboratory of Breast Cancer, Discipline of Integrated Chinese and Western Medicine, the Research Center of Integrative Medicine, School of Basic Medical Sciences & the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China[b]Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China[c]Post-doctoral Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China[*1]Integrative Research Laboratory of Breast Cancer, Discipline of Integrated Chinese and Western Medicine, the Research Center of Integrative Medicine, School of Basic Medical Sciences & the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
推荐引用方式(GB/T 7714)：
Bowen Yang,Neng Wang,Shengqi Wang,et al.Network-pharmacology-based identification of caveolin-1 as a key target of Oldenlandia diffusa to suppress breast cancer metastasis[J].BIOMEDICINE & PHARMACOTHERAPY.2019,112:doi:10.1016/j.biopha.2019.108607.
APA：
Bowen Yang,Neng Wang,Shengqi Wang,Xiong Li,Yifeng Zheng...&Zhiyu Wang.(2019).Network-pharmacology-based identification of caveolin-1 as a key target of Oldenlandia diffusa to suppress breast cancer metastasis.BIOMEDICINE & PHARMACOTHERAPY,112,
MLA：
Bowen Yang,et al."Network-pharmacology-based identification of caveolin-1 as a key target of Oldenlandia diffusa to suppress breast cancer metastasis".BIOMEDICINE & PHARMACOTHERAPY 112.(2019)
