DNA-PK inhibition synergizes with oncolytic virus M1 by inhibiting antiviral response and potentiating DNA damage

Xiao Xiao, Jiankai Liang, Chunlong Huang, Kai Li, Fan Xing, Wenbo Zhu, Ziqing Lin, Wencang Xu, Guangen Wu, Jifu Zhang, Xi Lin, Yaqian Tan, Jing Cai, Jun Hu, Xueqin Chen, Youwei Huang, Zixi Qin, Pengxin Qiu, Xingwen Su, Lijun Chen, Yuan Lin (), Haipeng Zhang () and Guangmei Yan ()
Additional contact information
Xiao Xiao: University of South China
Jiankai Liang: Sun Yat-sen University
Chunlong Huang: Sun Yat-sen University
Kai Li: The Sixth Affiliated Hospital of Sun Yat-sen University
Fan Xing: Sun Yat-sen University
Wenbo Zhu: Sun Yat-sen University
Ziqing Lin: Guangzhou Virotech Pharmaceutical Co., Ltd
Wencang Xu: Guangzhou Virotech Pharmaceutical Co., Ltd
Guangen Wu: Guangzhou Virotech Pharmaceutical Co., Ltd
Jifu Zhang: Guangzhou Virotech Pharmaceutical Co., Ltd
Xi Lin: Jinan University
Yaqian Tan: Sun Yat-sen University
Jing Cai: Sun Yat-sen University
Jun Hu: Sun Yat-sen University
Xueqin Chen: Jinan University
Youwei Huang: Jinan University
Zixi Qin: Jinan University
Pengxin Qiu: Sun Yat-sen University
Xingwen Su: Sun Yat-sen University
Lijun Chen: Sun Yat-sen University
Yuan Lin: Sun Yat-sen University
Haipeng Zhang: Jinan University
Guangmei Yan: Sun Yat-sen University

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract Oncolytic virotherapy is a promising therapeutic strategy that uses replication-competent viruses to selectively destroy malignancies. However, the therapeutic effect of certain oncolytic viruses (OVs) varies among cancer patients. Thus, it is necessary to overcome resistance to OVs through rationally designed combination strategies. Here, through an anticancer drug screening, we show that DNA-dependent protein kinase (DNA-PK) inhibition sensitizes cancer cells to OV M1 and improves therapeutic effects in refractory cancer models in vivo and in patient tumour samples. Infection of M1 virus triggers the transcription of interferons (IFNs) and the activation of the antiviral response, which can be abolished by pretreatment of DNA-PK inhibitor (DNA-PKI), resulting in selectively enhanced replication of OV M1 within malignancies. Furthermore, DNA-PK inhibition promotes the DNA damage response induced by M1 virus, leading to increased tumour cell apoptosis. Together, our study identifies the combination of DNA-PKI and OV M1 as a potential treatment for cancers.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06771-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06771-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-06771-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().