RESUMO
Pancreatic cancer remains one of the most lethal types of cancer. Latestage 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 ßelemene. Although peritoneal perfusion of ßelemene attenuates the progression of malignant effusion without severe adverse effects in the clinic, the underlying molecular mechanism underlying the activity of ßelemene against peritoneum effusion remains unclear. In the present study, a network pharmacology approach was undertaken to explore the mechanism of ßelemene against peritoneum effusion. Particularly, the networks of ßelemene and pancreatic cancer target genes were constructed based on the BATMANTCM and DigSee databases, respectively. Thirtythree genes, including hypoxia inducible factor 1 subunit α (HIF1A), were discovered in both networks. A potential interaction of ßelemene with HIF1A was revealed by molecular docking simulation and coexpression analysis of pancreatic cancer datasets from The Cancer Genome Atlas (TCGA) database. Additionally, experimental validation by MTT assay demonstrated that ßelemene suppressed proliferation of PANC1 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 ßelemene. Overall, this study proposes a potential molecular mechanism illustrating that ßelemene 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.
