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

• Published in: Oncology reports Vol. 42; no. 6; pp. 2561 - 2571
• Main Authors: Zhu, Junqiu, Li, Bo, Ji, Yongsuo, Zhu, Linglin, Zhu, Yanfei, Zhao, Hong
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications UK Ltd 01.12.2019; D.A. Spandidos
• Subjects: Aged; Angiogenesis; Antigens; Apoptosis; Ascites - etiology; Ascitic Fluid - cytology; Ascitic Fluid - drug effects; Cancer therapies; Cell Line, Tumor; Chemotherapy; Chinese medicine; Datasets as Topic; Drug Discovery - methods; Drug Screening Assays, Antitumor; FDA approval; Gene Expression Regulation, Neoplastic - drug effects; Gene Regulatory Networks - drug effects; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Kaplan-Meier Estimate; Liver cancer; Male; Metastasis; Molecular Docking Simulation; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Patients; Peritoneal Neoplasms - genetics; Peritoneal Neoplasms - mortality; Peritoneal Neoplasms - prevention & control; Peritoneal Neoplasms - secondary; Peritoneum - pathology; Pharmacology; Protein expression; Protein Interaction Mapping - methods; Protein Interaction Maps - drug effects; Protein Interaction Maps - genetics; Proteins; Sesquiterpenes - pharmacology; Sesquiterpenes - therapeutic use; Signal Transduction - drug effects; Signal Transduction - genetics; Simulation; Studies; Tumors; Vascular Endothelial Growth Factor A - metabolism; China
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2019.7360

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.