The glioblastoma suppression effect of recombinant Newcastle disease virus harboring the PTEN gene delivered intravenously to a U87 MG PTEN mutant glioblastoma cell-bearing orthotropic mouse model

Abstract

Abstract Glioblastoma (GBM) is the most malignant brain tumor and is associated with a low survival and high recurrence rate. Deletions and mutations in phosphatase and tensin homolog (PTEN), a tumor suppressor gene, are associated with therapeutic resistance. In this study, we constructed a recombinant Newcastle disease virus (rNDV) overexpressing human PTEN (rNDV-PTEN) in GBM cells. PTEN overexpression decreased cell proliferation and migration and induced apoptosis in U87 MG cells. GBM tumorigenesis was also examined in vivo using orthotopic mouse models. rNDV and rNDV-PTEN crossed the blood–brain barrier to reach the GBM in the brain. A reduction in GBM size in mice treated intravenously with rNDV-PTEN was confirmed by in vivo and magnetic resonance imaging. PTEN overexpression increased mTOR dephosphorylation and decreased autophagy. As a result, the levels of pre-apoptotic markers such as caspases 3, 8, and 9 and Bax were increased in PTEN-overexpressing GBM cells. Taken together, these results suggest that PTEN overexpression via rNDV treatment promotes apoptosis of GBM cells by disrupting mTOR signaling and autophagy, suggesting a new strategy to treat GBM.