Piperine has immunomodulatory and anti-inflammatory properties, and its potential in treating cervical cancer needs further exploration. Using data from The Cancer Genome Atlas (TCGA), we identified immune-related differentially expressed genes (IRDEGs) in cervical cancer. Predicted targets of piperine were compared with cervical cancer-associated genes from various databases. Protein-protein interaction (PPI) network analysis, enrichment of GO and KEGG pathways, and molecular docking were performed. Kaplan-Meier survival analysis was done to assess prognostic significance. In vitro and in vivo experiments were conducted to confirm findings. We obtained 403 IRDEGs, 125 piperine targets, and 7037 cervical cancer genes. PPI network analysis revealed potential targets and pathways regulated by piperine. Molecular docking showed good binding activity of piperine with specific targets. In vitro, piperine inhibited cervical cancer cell proliferation, migration, and invasion, and promoted apoptosis. In vivo, piperine suppressed tumor growth and downregulated expression of IL-1β and NLRP3 in tumor cells. Piperine also downregulated expression of IL-17A, IL-21, IL-22, and RORγt, and decreased the number of Th17 cells in tumor tissues. Piperine may inhibit cervical cancer progression through modulation of Th17 cell activation mediated by the NLRP3/IL-1β axis. Further studies are warranted to explore the potential of piperine as an immunomodulatory agent in cervical cancer treatment.
Keywords: Cervical cancer; IL-1β; NLRP3; Th17 cell; network pharmacology; piperine.