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The poly (ADP-ribose) polymerase inhibitor rucaparib suppresses proliferation and serves as an effective radiosensitizer in cervical cancer

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Summary

Objectives Our goal was to investigate the effects of rucaparib on the proliferation of cervical cancer cells and sensitivity to radiotherapy. Methods We used the human cervical cancer cell lines Hela and Siha and evaluated their viability and activity using various methods. Cellular proliferation was assessed by CCK-8 and clonogenic assays after treatment with rucaparib. Cell cycle analysis was performed using propidium iodide staining. Western immunoblotting analysis was used to detect the expression of cyclin D1 and CDK4. Immunofluorescence staining assay was performed to detect the expression of the DNA injury marker ץ-H2AX after treatment with rucaparib and radiotherapy. Animal experiments were also performed to evaluate tumor size after treatment with rucaparib. Immunohistochemistry was performed to analyze the expression of Ki-67. Results Rucaparib suppressed proliferation, induced G2/M phase arrest, and reduced the expression of cyclin D1 and CDK4 in cervical cancer cells. When rucaparib was combined with radiotherapy in cervical cancer cells, clone formation decreased significantly and G2/M phase arrest was accentuated. The expression of the DNA-damage marker ץ-H2AX was increased significantly, and rucaparib suppressed tumor growth in vivo. Conclusions Rucaparib exerts significant anti-proliferative effects and can serve as an effective radiosensitizer in cervical cancer, suggesting its candidacy in cervical cancer treatment and worthiness for further investigation.

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Acknowledgments

We would like to thank LetPub (www.letpub.com) for providing linguistic assistance during the preparation of this manuscript.

Funding

The work was supported by the Department of Health and Planning Commission in Wuxi, the China. The work was also supported by the Department of Affilited Hospital of Jiangnan University in Wuxi, the China.

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Authors and Affiliations

  1. Jiangnan University, Jiangsu Wuxi, 214000, China

    Mei Tang, Qiuli Liu, Ling Chen & Xueqing Yang

  2. Affilited Hospital of Jiangnan University, Huihe Road No.200, Wuxi, 214062, Jiangsu Province, China

    Leyuan Zhou, Jinjin Yu & Yuan Wang

  3. Affilited Hospital of Zhengzhou University, East Road No.1, Zhengzhou, 450000, Henan Province, China

    Haifeng Qiu

Authors
  1. Mei Tang
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  2. Qiuli Liu
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Corresponding authors

Correspondence to Yuan Wang or Haifeng Qiu.

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Conflict of Interest

Author Mei Tang declares that he has no conflict of interest.

Author Qiuli Liu declares that he has no conflict of interest.

Author Leyuan Zhou declares that he has no conflict of interest.

Author Ling Chen declares that he has no conflict of interest.

Author Xueqing Yang declares that he has no conflict of interest.

Author Jinjin Yu declares that he has no conflict of interest.

Author Yuan Wang declares that he has no conflict of interest.

Author Haifeng Qiu declares that he has no conflict of interest.

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This article does not contain any studies with human participants performed by any of the authors. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Tang, M., Liu, Q., Zhou, L. et al. The poly (ADP-ribose) polymerase inhibitor rucaparib suppresses proliferation and serves as an effective radiosensitizer in cervical cancer. Invest New Drugs 37, 65–75 (2019). https://doi.org/10.1007/s10637-018-0616-7

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  • DOI: https://doi.org/10.1007/s10637-018-0616-7

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