Recombinant Newcastle disease virus expressing P53 demonstrates promising antitumor efficiency in hepatoma model. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: An, Ying; Liu, Tianyan; He, Jinjiao; Wu, Hongsong; Chen, Rui; Liu, Yunye; Wu, Yunzhou; Bai, Yin; Guo, Xiaochen; Zheng, Qi; Liu, Chang; Yin, Jiechao; Li, Deshan; Ren, Guiping
• Is Part Of: Journal of biomedical science. Volume 23:Issue 1(2016)
• Page Start: 1
• Page End: 10
• Publication Date: 2016-12
• Subjects: Recombinant NDV -- P53 -- Gene therapy -- Anti-tumor; Medical sciences -- Periodicals; 610.28
• DOI: 10.1186/s12929-016-0273-0
• Languages: English
• ISSNs: 1021-7770

Abstract

Abstract Background Numerous 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. Results In 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. Conclusion rNDV-P53 is a potent candidate for carcinoma therapy especially for hepatocarcinoma.