Affiliation:
1. Yunnan Branch, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College
2. Yuxi Normal University
Abstract
Abstract
Resina draconis(RD), is known as the "holy medicine for promoting blood circulation", which is shown to possess anti-tumor properties in various types of cancer include Breast cancer(BC), however, the underlying mechanism is not well understood. To explore the potential mechanism of RD against BC using network pharmacology and experimental validation. Data on bioactive compounds, potential targets of RD, related genes of BC, were obtained from multiple public databases. Gene ontology (GO) and KEGG pathway analysis were performed via the DAVID database. The protein interaction was download from STRING database. The mRNA, protein expression levels and survival analysis of the hub targets were analyzed using UALCAN, HPA, Kaplan-Meier Mapper, and cBioPortal databases. Subsequently, molecular docking was used to verify the selected key ingredients and hub targets. Finally, the predicted results of network pharmacology methods were verified by cells experiments. In total, 160 active ingredients were obtained, 148 RD target genes for the treatment of BC were identified. KEGG pathway analysis indicated that RD could exert its therapeutic effects on BC by regulating multiple pathways. Of these, the PI3K-AKT pathway could play an important role. In addition, RD could treat BC by regulating hub targets that were determined with the PPI interaction network. The validation in different databases showed that may AKT1, ESR1, HSP90AA1, CASP3, SRC and MDM2 be involved in the carcinogenesis and progression of BC, as well as ESR1, IGF1 and HSP90AA1 were correlated to worse overall survival (OS) in BC. Molecular docking results showed that flavonoids compounds have good binding activity with the hub targets. Therefore, the sanguis draconis flavones (SDF) were selected for subsequent cell experiments. The experimental results showed that SDF significantly inhibits the cell cycle and cell proliferation through the PI3K-AKT pathway and that it can induce apoptosis of MCF-7 cells. The study has preliminarily discussed the active ingredients, potential targets, and molecular mechanism of RD against BC; and RD could exert its therapeutic effects on BC by regulating PI3K/AKT pathway and related gene targets. Importantly, our work could provide a theoretical basis for further study on its complex anti-BC mechanism.
Publisher
Research Square Platform LLC
Reference80 articles.
1. The Lingering Mysteries of Metastatic Recurrence in Breast Cancer;Riggio AI;Br. J. Cancer.,2021
2. Sung, H. et al. Global Cancer Statistics 2020: Globocan Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. Ca-Cancer J. Clin. 71, 209–249 (2021).
3. Breast Cancer Heterogeneity through the Lens of Single-Cell Analysis and Spatial Pathologies;Zhao N;Semin. Cancer Biol.,2022
4. Breast Cancer Treatment;Waks AG;Jama-J. Am. Med. Assoc.,2019
5. Breast Cancer: Presentation, Investigation and Management;Katsura C;Br. J. Hosp. Med.,2022