The phosphatase and tensin homolog gene inserted between NP and P gene of recombinant New castle disease virus oncolytic effect test to glioblastoma cell and xenograft mouse model

Virol J. 2022 Jan 29;19(1):21. doi: 10.1186/s12985-022-01746-w.

Abstract

Background: Glioblastoma is one of the most serious brain cancer. Previous studies have demonstrated that PTEN function disorder affects the causing and exacerbation of glioblastoma. Newcastle disease virus (NDV) has been studied as a cancer virotherapeutics. In this study, PTEN gene was delivered to glioblastoma by recombinant NDV (rNDV) and translated into protein at the cytoplasm of the glioblastoma.

Methods: We did comparison tests PTEN protein expression efficiency and oncolytic effect depend on the PTEN gene insertion site at the between NP and P genes and the between P and M gene. PTEN protein mRNA transcription, translation in glioblastoma cell, and functional PTEN protein effect of the rNDV in vitro and in vivo test performed using western blotting, RT-qPCR, MTT assay, and Glioblastoma xenograft animal model test.

Results: The result of this study demonstrates that rNDV-PTEN kills glioblastoma cells and reduces cancer tissue better than rNDV without the PTEN gene. In molecular immunological and cytological assays, PTEN expression level was high at located in the between NP and P gene, and PTEN gene was successfully delivered to the glioblastoma cell using rNDV and PTEN gene translated to functional protein and inhibits hTERT and AKT gene.

Conclusions: PTEN gene enhances the oncolytic effect of the rNDV. And our study demonstrated that NP and P gene site is better than P and M gene site which is commonly and conventionally used. PTEN gene containing rNDV is a good candidate virotherapeutics for glioblastoma.

Keywords: Glioblastoma; New castle disease virus; Oncolysis; Phosphate and tensin homolog; Tumor suppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / therapy
  • Brain Neoplasms* / virology
  • Cell Line, Tumor
  • Glioblastoma*
  • Heterografts
  • Humans
  • Mice
  • Newcastle disease virus* / genetics
  • Newcastle disease virus* / metabolism
  • Oncolytic Virotherapy*
  • PTEN Phosphohydrolase* / genetics
  • PTEN Phosphohydrolase* / metabolism
  • Phosphoric Monoester Hydrolases / metabolism

Substances

  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase