Background: Resveratrol is a natural polyphenol commonly seen in foods. It has demonstrated an inhibitive effect on endometrial cancer, but the molecular action is still not known.
Objective: We aimed to use network pharmacology to systematically study the possible mechanisms of resveratrol’s pharmacological effects on type I endometrial cancer.
Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) were used to predict resveratrol’s possible target genes. They were then converted to UniProt gene symbols. Simultaneously, type I endometrial cancer-related target genes were collected from GeneCards. All data were pooled to identify common target genes. The protein-protein interaction (PPI) network was constructed and further analyzed via STRING Online Database. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were also performed afterward. To visualise resveratrol's overall pharmacological effects on type I endometrial cancer, a network of drug components-target gene-disease (CTD) was constructed. Then, we performed in silico molecular docking study to validate the possible binding conformation between resveratrol and candidate targets.
Results: There are 150 target genes of resveratrol retrieved after UniProt conversion; 122 of them shared interaction with type I endometrial cancer. Some important oncogenes and signaling pathways are involved in the process of resveratrol’s pharmacological effects on endometrioid cancer. Molecular docking analysis confirmed that hydrogen bonding and hydrophobic interaction are the main interaction between resveratrol and its targets.
Conclusion: We have explored the possible underlying mechanism of resveratrol in antagonising type I endometrial cancer through a network pharmacology-based approach and in-silico verification. However, further experiments are necessary to add to the evidence identifying resveratrol as a promising anti-type I endometrial cancer agent.