Anticancer Effects of Herbal Medicines in Pancreatic Cancer Through Modulation of Steroid Hormone Response Proteins

Abstract Many individual herbs and herbal formulae have been demonstrated to provide safe and effective treatment for Pancreatic cancer (PC); however, the therapeutic mechanisms underlying their effects have not been fully elucidated. A total of 114 herbal formulae comprising 216 single herbal medicines used to treat PC were identified. Cluster analysis revealed a core prescription including four herbs [Glycyrrhizae Radix et Rhizome (Gan Cao), Codonopsis Radix (Dang Shen), Citri Reticulatae Pericarpium (Chen Pi), and Pinelliae Rhizoma (Ban Xia)] in combination to treat PC, and 295, 256, 141, and 365 potential targets were screened for each of these four herbs, respectively. PC-related proteins (n = 2940) were identified from the DisGeNET database. Finally, 44 overlapping targets of herbs and PC were obtained, representing potential targets of the herbal medicines for PC treatment. GO enrichment analysis indicated that targets common to herbs and PC primarily functioned in response to steroid hormones. KEGG pathway enrichment analysis indicated that the herbs may prevent PC by influencing apoptotic, p53, and PI3K/Akt signaling pathways. Further, molecular docking analysis indicated that of identified bioactive compounds, stigmasterol, phaseol, perlolyrine, shinpterocarpin, and licopyranocoumarin have good binding ability with proteins involved in responses to steroid hormones, while stigmasterol, phaseol, perlolyrine, and DIOP have good binding ability with PTGS2(also known as COX-2), ESR1, ESR2, AR, and PGR. Conclusion: The anti-PC activity of herbal medicines may be mediated via regulation of proteins with roles in responses to steroid hormones. This study provides further evidence supporting the potential for use of herbal medicines to treat PC.