beta-elemene and Pancreatic-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

Dendritic cell (DC) vaccine is a kind of treatment vaccine with clinical application potency. Functional cytokines can enhance anti-tumor immune response of dendritic cells. This study was to investigate the protective effects on murine pancreatic carcinoma by beta-elemene combined with bone marrow-derived dendritic cells (BM-DCs) modified with murine interleukin (IL)-23 gene.. The murine IL-23 cDNA was sub-cloned into dual-expression vector. DCs were pulsed with tumor cell lysate after modified by IL-23 gene. Mice were injected with IL-23-transfected DC vaccine, non-transfected DC vaccine, and sodium, respectively. The immune preventative and immunotherapeutic effects of DC vaccines on mice and the cytokine release in vivo were assessed. Effects of vaccine combined with beta-elemene on tumor growth and survival period of the mice were observed.. IL-23 protein apparently increased the antigen-presenting ability of DCs. After the vaccination of DC vaccines, IFN-gamma production in treatment group was significantly more than that of the control group (P<0.01), as well as, IL-4 production was less than that in the normal group (P<0.05). Tumor growth was obviously inhibited and the survival period of the mice was obviously prolonged in beta-elemene combined with DC vaccine group than in DC, beta-elemene, or control group (P<0.01).. IL-23-modified DC vaccines can enhance specific Th1-type and CTL response against pancreatic carcinoma cells, induce not only preventative immunity, but also auto-immunity against pancreatic carcinoma. Moreover, beta-elemene has great collaborative anti-tumor function.

Topics: Animals; Cancer Vaccines; Dendritic Cells; Female; Immunotherapy; Interferon-gamma; Interleukin-23; Interleukin-4; Mice; Mice, Inbred C57BL; Pancreatic Neoplasms; Random Allocation; Sesquiterpenes; Transfection