β-elemene inhibits the generation of peritoneum effusion in pancreatic cancer via suppression of the HIF1A-VEGFA pathway based on network pharmacology

Pancreatic cancer remains one of the most lethal types of cancer. Late-stage pancreatic cancer patients usually suffer peritoneum effusion, which severely compromises quality of life. Great efforts have been made concerning the treatment of peritoneum effusion, including treatment with β-elemene. Although peritoneal perfusion of β-elemene attenuates the progression of malignant effusion without severe adverse effects in the clinic, the underlying molecular mechanism underlying the activity of β-elemene against peritoneum effusion remains unclear. In the present study, a network pharmacology approach was undertaken to explore the mechanism of β-elemene against peritoneum effusion. Particularly, the networks of β-elemene and pancreatic cancer target genes were constructed based on the BATMAN-TCM and DigSee databases, respectively. Thirty-three genes, including hypoxia inducible factor 1 subunit α (HIF1A), were discovered in both networks. A potential interaction of β-elemene with HIF1A was revealed by molecular docking simulation and co-expression analysis of pancreatic cancer datasets from The Cancer Genome Atlas (TCGA) database. Additionally, experimental validation by MTT assay demonstrated that β-elemene suppressed proliferation of PANC-1 and BxPC3 cells and cells from peritoneum effusion in patients with pancreatic cancer. Furthermore, the protein expression levels of HIF1A and vascular endothelial growth factor A (VEGFA), as detected by western blotting, were reduced by β-elemene. Overall, this study proposes a potential molecular mechanism illustrating that β-elemene can block the HIF1A/VEGFA pathway, thereby inhibiting the generation of peritoneum effusion in pancreatic cancer based on network pharmacology analysis, and further highlights the importance of targeting the HIF1A/VEGF pathway as a therapeutic approach to treat peritoneum effusion in patients with pancreatic cancer.