China Oncology ›› 2021, Vol. 31 ›› Issue (2): 100-107.doi: 10.19401/j.cnki.1007-3639.2021.02.003

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Down-regulation of Ku86 inhibits cisplatin-induced chemotherapy sensitivity by regulating TOP1 and COPS5 in epithelial ovarian cancer

MA Qian 1, 2* , LIU Yixuan 1 , KAI Jinyan 1 , GUO Lin 1 , LU Renquan 1    

  1. 1. Department of Clinical Laboratory, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 2. Department of Clinical Laboratory, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710000, Shaanxi Province, China 
  • Online:2021-02-28 Published:2021-03-02
  • Contact: LU Renquan E-mail:

Abstract: Background and purpose: Ovarian cancer is the disease with the third highest incidence and the highest lethality among gynecological malignancies. Ovarian cancer has a poor prognosis because most patients are in advanced stages at the time of diagnosis and susceptible to resistance to platinum-based chemotherapy. Abnormal DNA repair is an important cause of platinum resistance. Targeting interference with DNA damage repair molecules may be a new way to improve the sensitivity to platinum chemotherapy. Ku86 is a key molecule involved in the process of non-homologous end joining (NHEJ), which can effectively repair DNA double-strand break (DSB). Methods: Immunohistochemical staining and cellular immunofluorescence were used to detect the localization of Ku86 in ovarian cancer tissues and cells. Ku86 was downregulated by RNAi technology, apoptosis was detected by flow cytometry after treatment with cisplatin, and IC 50 was detected by cell counting kit-8 (CCK-8) method. Western blot was used to detect and analyze the relationship between Ku86 and topoisomerase Ⅰ(TOP1) and the fifth component of the COP9 signalosome (COPS5). Results: This study found that downregulating Ku86 reduced the apoptosis caused by cisplatin and decreased the sensitivity of ovarian cancer cells to cisplatin. This effect of Ku86 on cisplatin in ovarian cancer drug sensitivity might be mediated by the regulation of TOP1 and COPS5. Conclusion: TOP1 and COPS5 are both important molecules related to DNA damage repair and can affect platinum sensitivity in chemotherapy. Our study found that downregulating Ku86 increased the expression of TOP1 and decreased the expression of COPS5. This study preliminarily elucidated the relationship between biomarkers related to platinum drug sensitivity in ovarian cancer. Ku86-targeted therapy may be an effective strategy to improve drug sensitivity in ovarian cancer.

Key words: Ku86, Topoisomerase Ⅰ, The fifth component of the COP9 signalosome, Cisplatin, DNA damage repair