Targeting RAD51 enhances chemosensitivity of adult T‑cell leukemia‑lymphoma cells by reducing DNA double‑strand break repair

Yang,Meng; Tian,Xiaoxue; Fan,Zhuoyi; Yu,Wenlei; Li,Zheng; Zhou,Jie; Zhang,Wenjun; Liang,Aibin

doi:10.3892/or.2019.7384

Targeting RAD51 enhances chemosensitivity of adult T‑cell leukemia‑lymphoma cells by reducing DNA double‑strand break repair

Authors:
- Meng Yang
- Xiaoxue Tian
- Zhuoyi Fan
- Wenlei Yu
- Zheng Li
- Jie Zhou
- Wenjun Zhang
- Aibin Liang
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Affiliations: Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R China
Published online on: October 22, 2019 https://doi.org/10.3892/or.2019.7384
Pages: 2426-2434
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

RAD51, is a key homologous recombination protein that repairs DNA damage and maintains gene diversity and stability. Previous studies have demonstrated that the over‑expression of RAD51 is associated with chemotherapy resistance of tumor cells to chemotherapy, and enhanced activity of DNA damage repair (DDR) systems contributes to resistance of adult T‑cell leukemia‑lymphoma (ATL) resistance to chemotherapy. Thus, targeting RAD51 is a potential strategy for the sensitization of ATL cells to chemotherapeutic drugs by inducing DNA damage. In general, cells can repair minor DNA damage through DDR; however, serious DNA damage may cause cell toxicity in cells which cannot be restored. In the present, down regulation of RAD51 by shRNA and imatinib sensitized Jurkat cells to etoposide by decreasing the activity of homologous recombination (HR). We found that the suppression of RAD51 by shRNA inhibited tumor cells proliferation and enhanced apoptosis of Jurkat cells after etoposide treatment. Importantly, downregulation of RAD51 by imatinib obviously increased the apoptosis of Jurkat cell after etoposide treatment. These results demonstrated that RAD51 may be of great value to as a novel target for the clinical treatment of adult T‑cell leukemia‑lymphoma (ATL), and it may improve the survival of leukemia patients.

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