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DDB2 increases radioresistance of NSCLC cells by enhancing DNA damage responses

  • Original Article
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Tumor Biology

Abstract

Radiotherapy resistance is one of the major factors limiting the efficacy of radiotherapy in lung cancer patients. The extensive investigations indicate the diversity in the mechanisms underlying radioresistance. Here, we revealed that DNA damage binding protein 2 (DDB2) is a potential regulator in the radiosensitivity of non-small cell lung cancer (NSCLC) cells. DDB2, originally identified as a DNA damage recognition factor in the nucleotide excision repair, promotes the survival and inhibits the apoptosis of NSCLC cell lines upon ionizing radiation (IR). Mechanistic investigations demonstrated that DDB2 is able to facilitate IR-induced phosphorylation of Chk1, which plays a critical role in the cell cycle arrest and DNA repair in response to IR-induced DNA double-strand breaks (DSBs). Indeed, knockdown of DDB2 compromised the G2 arrest in the p53-proficient A549 cell line and reduced the efficiency of homologous recombination (HR) repair. Taken together, our data indicate that the expression of DDB2 in NSCLC could be used as a biomarker to predict radiosensitivity of the patients. Targeting Chk1 can be used to increase the efficacy of radiotherapy in patients of NSCLC possessing high levels of DDB2.

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Acknowledgment

We thank Dr. Jeff Parvin (The Ohio State University) for providing HeLa-DR cells and pCBASce plasmids. This work was supported by National Institute of Health (CA151248 to Q.E.W.).

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Authors and Affiliations

  1. Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan, Hubei, 430079, China

    Ning Zou

  2. Department of Radiology, Division of Radiobiology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA

    Ning Zou, Guozhen Xie, Tiantian Cui, Amit Kumar Srivastava & Qi-En Wang

  3. Dublin Coffman High School, Dublin, OH, 43017, USA

    Guozhen Xie

  4. Department of Pharmacology, Weifang Medical University, Weifang, Shandong, 261053, China

    Meihua Qu

  5. Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA

    Linlin Yang

  6. Department of Gastrointestinal Oncology, Hubei Cancer Hospital, Wuhan, Hubei, 430079, China

    Shaozhong Wei

  7. Oncology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China

    Yanfang Zheng

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  1. Ning Zou
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  2. Guozhen Xie
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Correspondence to Yanfang Zheng or Qi-En Wang.

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This work was supported by National Institute of Health (CA151248 to Q.E.W.).

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Zou, N., Xie, G., Cui, T. et al. DDB2 increases radioresistance of NSCLC cells by enhancing DNA damage responses. Tumor Biol. 37, 14183–14191 (2016). https://doi.org/10.1007/s13277-016-5203-y

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  • DOI: https://doi.org/10.1007/s13277-016-5203-y

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