Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer
Cheng Chang1, Ruiying Jia2, Bin Fang3
1General Surgery Department, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, 266011, China.
Objectives:
This study aims to assess the potential mechanism of rutin to treat triple-negative breast cancer (TNBC) based on network pharmacology followed by in vitro experiments.
Methods:
The potential rutin targets were predicted, and the DisGeNET database was used to obtain the disease targets. The intersection targets were identified with Venny 2.1 software, with the String database subsequently used as input to produce the "drug-target-disease" visual network employing Cytoscape 3.7.2. Gene ontology. Kyoto Encyclopaedia of Genes and Genomes analyses were performed for intersection targets, while AutoDock Vina was used for molecular docking and visualization. Cell viability was assessed using the Colorimetric CCK-8 test, and apoptosis was analyzed using PI/Annexin V. The predicted core targets were confirmed by qPCR and western blotting assays.
Results:
EGFR, IL6, TNF, and INS were found as the primary targets. The molecular docking analysis revealed the rutin interaction with the core targets. The in vitro results confirmed that rutin inhibited the growth of the MDA-MB-231 cell line. Rutin also induced cell death and decreased the expressions of IL6, TNF, INS, and EGFR.
Conclusion:
Rutin's multi-target effects and molecular mechanism for treating TNBC were confirmed through preliminary results. The results provide a theoretical base for rutin's possible function in breast cancer treatment.
Insights
Rutin shows potential for treating triple-negative breast cancer (TNBC) by targeting multiple pathways, including EGFR, IL6, TNF, and INS. This study confirms its anti-cancer effects and provides a basis for its use in breast cancer therapy.
Area of Science:
- Pharmacology
- Oncology
- Computational Biology
Background:
- Triple-negative breast cancer (TNBC) remains a challenging subtype with limited targeted therapies.
- Rutin, a natural flavonoid, has demonstrated potential anti-cancer properties.
- Understanding the molecular mechanisms of rutin in TNBC is crucial for therapeutic development.
Purpose of the Study:
- To elucidate the potential mechanism of rutin in treating triple-negative breast cancer (TNBC) using network pharmacology.
- To validate the predicted targets and anti-cancer effects of rutin through in vitro experiments.
- To provide a theoretical foundation for rutin's application in breast cancer treatment.
Main Methods:
- Network pharmacology was employed to predict rutin's targets and construct a drug-target-disease network.
- Bioinformatics tools (DisGeNET, String, Cytoscape) and molecular docking (AutoDock Vina) were utilized for target identification and interaction analysis.
- In vitro assays, including CCK-8, PI/Annexin V staining, qPCR, and western blotting, were performed to validate findings in the MDA-MB-231 cell line.
Main Results:
- Key targets including EGFR, IL6, TNF, and INS were identified for rutin's action in TNBC.
- Molecular docking confirmed the interaction between rutin and these core targets.
- In vitro studies demonstrated that rutin inhibits MDA-MB-231 cell proliferation, induces apoptosis, and downregulates the expression of IL6, TNF, INS, and EGFR.
Conclusions:
- Rutin exhibits multi-target effects and a defined molecular mechanism for treating TNBC.
- The study provides preliminary evidence supporting rutin's therapeutic potential in breast cancer.
- These findings lay the groundwork for further investigation into rutin as a novel TNBC treatment.
