NDV-D90 suppresses growth of gastric cancer and cancer-related vascularization

Oncotarget. 2017 May 23;8(21):34516-34524. doi: 10.18632/oncotarget.16563.

Abstract

Recent reports suggest promises on using oncolytic Newcastle disease viruses (NDV) to treat different cancers, while the effects of a NDV-D90 strain on gastric cancer remain unknown. Here we showed that NDV-D90 induced gastric cancer cell apoptosis in a dose-dependent manner in 3 gastric cancer cell lines BGC-823, SGC-7901 and MKN-28. Pronounced reduction in cell invasion was detected in NDV-D90-treated BGC-823 and SGC-7901 cells, but not in MKN-28 cells. The increases in cell apoptosis and reduction in cell growth in NDV-D90-treated gastric cancer cells seemingly resulted from augmentation of p38 signaling and suppression of ERK1/2 and Akt signaling. In vivo, orthotopic injection of NDV-D90 impaired tumor growth and induced intratumoral necrosis. Tumor cells that had been pre-treated with NDV-D90 showed defect in development of implanted tumor. Moreover, NDV-D90 appeared to reduce gastric tumor vascularization, possibly through suppression of vascular endothelial growth factor A and Matrix Metallopeptidase 2. Together, our data suggest that NDV-D90 may have potential anti-cancer effects on gastric cancer.

Keywords: apoptosis; gastric cancer; matrix metallopeptidase 2 (MMP-2); newcastle disease viruses (NDV); vascular endothelial growth factor A (VEGF-A).

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Humans
  • MAP Kinase Signaling System
  • Mice
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / therapy*
  • Newcastle disease virus / growth & development*
  • Oncolytic Virotherapy / methods*
  • Stomach Neoplasms / blood supply
  • Stomach Neoplasms / therapy*
  • Xenograft Model Antitumor Assays