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Published on: August 23, 2019
NDV-D90 suppresses growth of gastric cancer and cancer-related vascularization
Hong Sui1, Kaibing Wang2, Rui Xie1
1Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150040, China.
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.
Insights
Newcastle disease virus (NDV)-D90 shows potential as an anti-gastric cancer therapy. This oncolytic virus effectively reduced tumor growth, induced cell death, and inhibited invasion in preclinical models.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Oncolytic viruses are emerging as promising cancer therapeutics.
- Newcastle disease virus (NDV) has shown potential against various cancers.
- The efficacy of the ND-D90 strain against gastric cancer is not yet understood.
Purpose of the Study:
- To investigate the effects of the NDV-D90 strain on gastric cancer cells and tumor growth.
- To explore the underlying molecular mechanisms of NDV-D90's anti-cancer activity.
Main Methods:
- In vitro studies using three gastric cancer cell lines (BGC-823, SGC-7901, MKN-28) treated with NDV-D90.
- Analysis of cell apoptosis, invasion, and signaling pathways (p38, ERK1/2, Akt).
- In vivo studies involving orthotopic injection of NDV-D90 in a gastric cancer model.
Main Results:
- NDV-D90 induced dose-dependent apoptosis and reduced cell growth in gastric cancer cell lines.
- NDV-D90 significantly inhibited cell invasion in BGC-823 and SGC-7901 cells.
- In vivo, NDV-D90 impaired tumor growth, induced necrosis, and reduced tumor vascularization.
- Observed effects were linked to modulation of p38, ERK1/2, and Akt signaling pathways, and suppression of VEGF-A and MMP-2.
Conclusions:
- NDV-D90 demonstrates significant anti-cancer effects against gastric cancer in vitro and in vivo.
- The virus induces apoptosis, inhibits invasion, and reduces tumor vascularization.
- NDV-D90 warrants further investigation as a potential therapeutic agent for gastric cancer.
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