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Abstract
BackgroundNumerous studies have demonstrated that the NDV-mediated gene therapy is a promising new approach for treatment of cancers. P53 plays a vital role in tumor suppression and surveillance. Therefore, we hypothesize that a recombinant NDV expressing P53 would be an ideal agent for the hepatoma therapy.ResultsIn the essay, the human P53 gene was incorporated into the genome of a lentogenic strain (named rNDV-P53), which did not affect viral replication kinetics and magnitude in HepG2 cells. Compared to the vehicle virus, rNDV-P53 increased cell growth suppressor ratio and early apoptosis by 2 folds, and decreased the mitochondrial membrane potential in HepG2 cells. In vivo studies, treatment with rNDV-P53 reduced tumor volume of tumor-bearing mice by more than 4 folds, tumor weight by more than 5 folds comparing with rNDV. The 120-day survival rate of rNDV-P53-treated mice was 75 %, survival rate of rNDV-treated mice was 12.5 %. TUNEL analysis showed a significant increase in the apoptosis rate in the tumor tissues of rNDV-P53-treated mice than that of rNDV-treated mice. Moreover, serum chemistries revealed an insignificant change of blood urea nitrogen (BUN), creatinine levels, alanine aminotransferase (ALT) and aspartate transaminase (AST) in rNDV-P53-treated group compared to normal mice, suggesting treatment with the recombinant virus was not toxic.ConclusionrNDV-P53 is a potent candidate for carcinoma therapy especially for hepatocarcinoma.
Highlights
Numerous studies have demonstrated that the Newcastle disease virus (NDV)-mediated gene therapy is a promising new approach for treatment of cancers
The high titers of rNDV-P53 suggested the successful generation of the recombinant NDV virus
The results showed that apoptosis percentages of rNDV group and rNDV-P53 were 10.4 % and 21.1 % respectively, which indicated that virus rNDV-P53 were more effective in inducing apoptosis in the HepG2 cells (Fig. 3b)
Summary
Numerous studies have demonstrated that the NDV-mediated gene therapy is a promising new approach for treatment of cancers. We hypothesize that a recombinant NDV expressing P53 would be an ideal agent for the hepatoma therapy. NDV was proposed as a promising anticancer agent [4,5,6,7], it is prone to replicate in human tumor cells and cause oncolytic effects but not in normal cells [8,9,10], The P53 tumor suppressor plays various roles in cellcycle control, apoptosis, senescence, DNA repair and modulating metabolic processes [16,17,18,19,20]. With the expression of these genes, cell death was induced by apoptosis [21, 22]. It has been proposed that the increased survival of tumor cells
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