- 作者: Ying An, Tianyan Liu, Jinjiao He, Hongsong Wu, Rui Chen, Yunye Liu, Yunzhou Wu, Yin Bai, Xiaochen Guo, Qi Zheng, Chang Liu, Jiechao Yin, Deshan Li and Guiping Ren
- 作者服務機構: 1. Biopharmaceutical Lab, College of Life Science, Northeast Agriculture University, Mucai Street 59, Xiangfang district, Harbin, People’s Republic of China
- 中文摘要: --
- 英文摘要:
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. - 中文關鍵字: --
- 英文關鍵字: Recombinant NDV, P53, Gene therapy, Anti-tumor