Citation: Tong Guo, Xiuli Liu, Zhikun Zhang, Yiqun Luo, Tong Li, Lan Li, Huixue Wang, Yong Huang, Jian He, Qiaoying Chen, Yongxiang Zhao, Lu Gan, Liping Zhong. A recombinant Newcastle disease virus expressing MMP8 promotes oncolytic efficacy[J]. Chinese Chemical Letters, ;2021, 32(12): 3962-3966. doi: 10.1016/j.cclet.2021.05.001 shu

A recombinant Newcastle disease virus expressing MMP8 promotes oncolytic efficacy

National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Biotargeting Theranostics, Guangxi Medical University, Nanning 530021, China

yongxiang_zhao@126.com

gxmuganlu@126.com

zhong_liping@163.com

Received Date: 9 March 2021
Revised Date: 30 April 2021
Accepted Date: 6 May 2021
Available Online: 14 May 2021

Figures(5)

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.
- Oncolytic virus,
- Newcastle disease virus,
- Matrix metalloproteinase 8,
- Extracellular matrix,
- Cancer treatment
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