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

Sung Hoon Jang,Hyun Jang,Bo-Kyoung Jung,Yong Hee An

doi:10.1186/s12985-022-01746-w

Abstract

BackgroundGlioblastoma 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.MethodsWe 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.ResultsThe 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.ConclusionsPTEN 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.

Highlights

Glioblastoma or glioma, one of the most serious brain cancer originates from glial cells that is a fatal tumor in the human central nervous system [1, 2]
In the 1950s velogenic strain of Newcastle disease virus (NDV) has been used to cancer-killing effect test even some of the oncolytic effects test was doing in Human patients
The growth dynamics curve shows that the two recombinant NDV (rNDV) viruses, one is having Phosphatase and tensin homolog (PTEN) gene Position “1”, but both of the recombinant viruses’ growths have no significant difference

Summary

Introduction

Glioblastoma or glioma, one of the most serious brain cancer originates from glial cells that is a fatal tumor in the human central nervous system [1, 2]. In the 2000s many scientists start using a lentogenic strain of NDV used to developing as an oncolytic virus This lentogenic strain has defects not strong cancer cell killing effect or tumor suppress effect compare with velogenic strain and the reason is lentogenic strain show lysogenic virus-like does not occur reinfection to neighbor cancer cell after the first infection. Several cancer cell killing and tumor suppress gene containing recombinant NDV virus has been constructed and used to test anticancer effect test include clinical trial This kind of progress successfully makes good results comparing to just attenuated NDV vaccine strain used previous test [18]. PTEN gene was delivered to glioblastoma by recombinant NDV (rNDV) and translated into protein at the cytoplasm of the glioblastoma

Methods

Results

Discussion

Conclusion