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Research Article
Newcastle Disease Virus Expressing an Angiogenic Inhibitor Exerts an Enhanced Therapeutic Efficacy in Colon Cancer Model
Deshan Li
Northeast Agricultural University
Corresponding Author
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Numerous studies demonstrate that the NDV-mediated gene therapy is a promising new approach for treatment of cancer. VEGF-Trap plays a vital role in anti-angiogenesis. Therefore, we hypothesize that a recombinant NDV (rNDV) expressing VEGF-Trap would be an ideal agent for the colon cancer therapy. In this study, VEGF-Trap gene was incorporated into the genome of rNDV (named rNDV-VEGF-Trap). rNDV-VEGF-Trap reduced cell growth ratio by 85.37% and migration ratio by 87.9% in EA.hy926 cells. In vivo studies, treatment with rNDV-VEGF-Trap reduced tumor volume of CT26-bearing mice by more than 3 folds and tumor weight by more than 4 folds. Immunohistochemistry analysis of CD34 showed rNDV-VEGF-Trap significantly decreased the number of vascular endothelial cells in the tumor tissues of the tumor-bearing mice. Moreover, Western blot analysis demonstrated that treatment with rNDV-VEGF-Trap significantly decreased the phosphorylation levels of AKT, ERK1/2 and STAT3 and increased the expression levels of P53, BAX and cleaved caspase-3 in the tumor tissue. In addition, to evaluate the toxicity of VEGF-Trap, serum chemistries were analyzed. The results showed that rNDV-VEGF-Trap caused insignificant changes of creatinine levels, alanine aminotransferase (ALT) and aspartate transaminase (AST). Futhermore, administration of rNDV-VEGF-Trap did not cause the diarrhoea，decreased appetite, weight decrease and haemorrhage of the experimental mice. These data suggest that rNDV-VEGF-Trap exhibits an enhanced inhibition of CT26-bearing mice by enhancing anti-angiogenesis and apoptosis. rNDV-VEGF-Trap is a potential candidate for carcinoma therapy especially for colon cancer.
Keywords
rNDV, VEGF-Trap, Gene therapy, Anti-angiogenesis, Colon cancer
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Research Article
Newcastle Disease Virus Expressing an Angiogenic Inhibitor Exerts an Enhanced Therapeutic Efficacy in Colon Cancer Model
Deshan Li
Northeast Agricultural University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 21 Jan, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Numerous studies demonstrate that the NDV-mediated gene therapy is a promising new approach for treatment of cancer. VEGF-Trap plays a vital role in anti-angiogenesis. Therefore, we hypothesize that a recombinant NDV (rNDV) expressing VEGF-Trap would be an ideal agent for the colon cancer therapy. In this study, VEGF-Trap gene was incorporated into the genome of rNDV (named rNDV-VEGF-Trap). rNDV-VEGF-Trap reduced cell growth ratio by 85.37% and migration ratio by 87.9% in EA.hy926 cells. In vivo studies, treatment with rNDV-VEGF-Trap reduced tumor volume of CT26-bearing mice by more than 3 folds and tumor weight by more than 4 folds. Immunohistochemistry analysis of CD34 showed rNDV-VEGF-Trap significantly decreased the number of vascular endothelial cells in the tumor tissues of the tumor-bearing mice. Moreover, Western blot analysis demonstrated that treatment with rNDV-VEGF-Trap significantly decreased the phosphorylation levels of AKT, ERK1/2 and STAT3 and increased the expression levels of P53, BAX and cleaved caspase-3 in the tumor tissue. In addition, to evaluate the toxicity of VEGF-Trap, serum chemistries were analyzed. The results showed that rNDV-VEGF-Trap caused insignificant changes of creatinine levels, alanine aminotransferase (ALT) and aspartate transaminase (AST). Futhermore, administration of rNDV-VEGF-Trap did not cause the diarrhoea，decreased appetite, weight decrease and haemorrhage of the experimental mice. These data suggest that rNDV-VEGF-Trap exhibits an enhanced inhibition of CT26-bearing mice by enhancing anti-angiogenesis and apoptosis. rNDV-VEGF-Trap is a potential candidate for carcinoma therapy especially for colon cancer.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the latest manuscript can be downloaded and accessed as a PDF.