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Roles of DNA polymerase ζ in the radiotherapy sensitivity and oxidative stress of lung cancer cells

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Abstract

Background

Previous reports stated that DNA polymerase ζ is highly expressed in lung cancer tissues. The present study aimed to investigate the roles and underlying mechanism of DNA polymerase ζ in lung cancer cell radioresistance.

Methods

The A549 and HCC827 cells were used to evaluate the effects of different doses of radiation on the mRNA and protein expressions of DNA polymerase ζ. Multiple assays, including PCR, western blot, flow cytometry, and EdU have been used to investigate the roles of DNA polymerase ζ on the cellular behaviors of A549 and HCC827 cells.

Results

The mRNA and protein expression of REV7L in A549 and HCC827 cells were significantly increased after 6 Gy irradiation compared to the control group. In A549 and HCC827 cells, over-expression of polymerase ζ decreased the radiosensitivity, inhibited cell apoptosis as well as reduced oxidative stress; while the knockdown of polymerase ζ showed the opposite effects. Knockdown of Polymerase ζ in xenograft animal models significantly decreased tumor size and induced oxidative stress of tumor tissues after irradiation.

Discussion

Our results provided a theoretical basis for targeting DNA polymerase ζ to improve the radiosensitivity of the lung cancer cells to radiotherapy.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was funded by Zhejiang Province public welfare Technology Application Research Plan (No. 2016C33224).

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, The Second Affiliated Hospital of Soochow University, NO.1055 Sanxiang Road, Suzhou, 215000, China

    Xialin Chen & Ming Chen

  2. Department of Radiation Oncology, Shaoxing People’s Hospital, NO. 568, North Zhongxing Road, Shaoxing, 312000, China

    Xialin Chen, Jianjiang Liu, Xueying Jin & Jianfang Wang

  3. Department of Radiation Oncology, The Second Hospital of Shaoxing, Shaoxing, 312000, China

    Rong Ji

  4. Department of Radiation Oncology, Minhang Branch of Cancer Hospital of Fudan University, Shanghai, 200240, China

    Hong Zhu

  5. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, 310000, China

    Ming Chen

Authors
  1. Xialin Chen
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  2. Rong Ji
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  3. Jianjiang Liu
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  4. Xueying Jin
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  5. Hong Zhu
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  6. Jianfang Wang
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  7. Ming Chen
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Contributions

XC and RJ were responsible for the organization and coordination of the trial and were the chief investigator; JL, XJ and HZ developed the trial design and responsible for the data analysis; JW and MC oversight and leadership responsibility for the research activity planning and execution, including mentorship external to the core team.

Corresponding authors

Correspondence to Jianfang Wang or Ming Chen.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Chen, X., Ji, R., Liu, J. et al. Roles of DNA polymerase ζ in the radiotherapy sensitivity and oxidative stress of lung cancer cells. Cancer Chemother Pharmacol 89, 313–321 (2022). https://doi.org/10.1007/s00280-021-04360-9

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  • DOI: https://doi.org/10.1007/s00280-021-04360-9

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