1. A recombinant Newcastle disease virus expressing MMP8 promotes oncolytic efficacy
- Author
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Qiaoying Chen, Liping Zhong, Yong Huang, Yongxiang Zhao, Huixue Wang, Yiqun Luo, Jian He, Xiuli Liu, Tong Guo, Lan Li, Lu Gan, Zhikun Zhang, and Tong Li
- Subjects
TUNEL assay ,viruses ,02 engineering and technology ,General Chemistry ,Biology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,biology.organism_classification ,01 natural sciences ,Molecular biology ,Newcastle disease ,Virus ,0104 chemical sciences ,Oncolytic virus ,Extracellular matrix ,Terminal deoxynucleotidyl transferase ,In vivo ,Viability assay ,0210 nano-technology - Abstract
Oncolytic virus is an emerging anti-cancer strategy. However, extracellular matrix (ECM), as a physical barrier, limits virus spread within the tumor. To overcome the obstacle, we constructed a recombinant Newcastle disease virus (NDV) expressing matrix metalloproteinase (MMP8) (NDV-MMP8) using with reverse genetic technology. In vitro, NDV-MMP8 was identified and verified by WB and ELISA. Cell viability was detected by CCK-8 assay. In vivo, we established two liver cancer xenograft models. NDV-MMP8 was injected into the tumor to observe the tumor volume and survival of mice. The changes in extracellular matrix were observed by Masson's trichrome staining. Virus expression in tumor tissues was detected by immunofluorescence assay. The virus titer in tumor tissues was detected by TCID50. Histopathological changes were detected by hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Intratumoral administration of NDV-MMP8 can effectively degrade ECM, promote the spread of the virus within the tumor, and reduce tumor growth rate. Therefore, the method of increasing intratumoral virus accumulation by degradation of the ECM to enhance the oncolytic effect has great potential for clinical application.
- Published
- 2021