beta-elemene and Peritoneal-Neoplasms

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.

Topics: Aged; Ascites; Ascitic Fluid; Cell Line, Tumor; Datasets as Topic; Drug Discovery; Drug Screening Assays, Antitumor; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Kaplan-Meier Estimate; Male; Molecular Docking Simulation; Pancreatic Neoplasms; Peritoneal Neoplasms; Peritoneum; Protein Interaction Mapping; Protein Interaction Maps; Sesquiterpenes; Signal Transduction; Vascular Endothelial Growth Factor A

Peritoneal metastasis is common in advanced gastric cancer patients and is typically associated with a worse prognosis. β-Elemene is a natural compound that can be isolated from the Curcuma wenyujin plant and has been widely used in China to treat a variety of cancers. However, the anti-metastatic impacts of β-elemene on gastric cancer remain unknown. In our study, we found that β-elemene significantly inhibited the migration and invasive capacity of gastric cells in vitro and inhibited the capacity of gastric cancer cells to peritoneally diffuse and metastasize in vivo. Mechanistically, we demonstrated that the anti-metastatic effects of β-elemene were exerted by downregulating the expression of Claudin-1. Furthermore, β-elemene was found to inhibit the metastatic capacity of cells by downregulating FAK phosphorylation, which regulated Claudin-1. Overall, our result revealed that β-elemene inhibited peritoneal metastases from gastric cancer by modulating the FAK/Claudin-1 pathway.

Topics: Animals; Cell Line, Tumor; Claudin-1; Female; Humans; Mice; Mice, Nude; Neoplasm Metastasis; Peritoneal Neoplasms; Phosphorylation; Sesquiterpenes; Signal Transduction; Stomach Neoplasms