Network-pharmacology-based identification of caveolin-1 as a key target of Oldenlandia diffusa to suppress breast cancer metastasis

Biomedicine & Pharmacotherapy

Shengqi Wang¹  Fengxue Zhang¹  Wenjie Mei²  Yifeng Zheng³  Zhiyu Wang³  Juxian Song³  Neng Wang³  Bowen Yang⁴  Min Li⁴  Yi Lin⁴  Xiong Li⁴ 

[1] 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;Post-doctoral Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China;the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China;;Integrative Research Laboratory of Breast Cancer, Discipline of Integrated Chinese and Western Medicine, the Research Center of Integrative Medicine, School of Basic Medical Sciences &

关键词: Oldenlandia diffusa;    Breast cancer;    Metastasis;    Network pharmacology;    Bioinformatics analysis;    Caveolin-1;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown