IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-06771-4.html
   My bibliography  Save this article

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

Author

Listed:
  • Xiao Xiao

    (University of South China
    Sun Yat-sen University)

  • 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
    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
    Sun Yat-sen University)

  • Haipeng Zhang

    (Jinan University
    Jinan University)

  • Guangmei Yan

    (Sun Yat-sen University)

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.

Suggested Citation

  • 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 & , 2018. "DNA-PK inhibition synergizes with oncolytic virus M1 by inhibiting antiviral response and potentiating DNA damage," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06771-4
    DOI: 10.1038/s41467-018-06771-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-06771-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-06771-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Li Guo & Cheng Hu & Yang Liu & Xiaoyu Chen & Deli Song & Runling Shen & Zhanzhen Liu & Xudong Jia & Qinfen Zhang & Yuanzhu Gao & Zhezhi Deng & Tao Zuo & Jun Hu & Wenbo Zhu & Jing Cai & Guangmei Yan & , 2023. "Directed natural evolution generates a next-generation oncolytic virus with a high potency and safety profile," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06771-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.