Cancer Management and Research (Jul 2019)

Silibinin restores the sensitivity of cisplatin and taxol in A2780-resistant cell and reduces drug-induced hepatotoxicity

  • Yang Z,
  • Pan Q,
  • Zhang D,
  • Chen JQ,
  • Qiu Y,
  • Chen X,
  • Zheng F,
  • Lin F

Journal volume & issue
Vol. Volume 11
pp. 7111 – 7122

Abstract

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Zhichun Yang,*,1 Qionghui Pan,*,2 Dingfang Zhang,3 Jianqiang Chen,3 Yinda Qiu,3 Xiaojing Chen,3 Feiyun Zheng,1 Feng Lin11Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of China; 2Department of Gynecology, Wenzhou People’s Hospital, Wenzhou 325027, Zhejiang, People’s Republic of China; 3School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, People’s Republic of China*These authors contributed equally to this workPurpose: Ovarian cancer is the most lethal cancer among all gynaecological malignancies. The combination theraputics of cisplatin and taxol is widely used in clinicals for ovarian cancer treatment. However, long-term use of cisplatin and taxol induces strong tolerance and hepatotoxicity. Since silibinin is a commonly used anti-hepatotoxic drug in Europe and Asia, the aim of this study was to determine whether silibinin could restore the sensitivity of combination use of cisplatin and taxol in drug-resistant human ovarian cancer cells and reduce drug-induced hepatotoxicity.Patients and methods: Normal hepatocyte LO2 cells and A2780/DDP cells were treated with silibinin, cisplatin, taxol, cisplatin and taxol plus silibinin for 48 h. Cell viability was determined by MTT and long-term proliferation assay, while apoptosis and cell cycle progression were assessed by flow cytometric analysis. DNA damage was evluated by immunofluorescence assays. The metastatic activity of A2780/DDP was determined by cell adhesion assay.Results: The addition of silibinin on cisplatin and/or toxal could sensitize the antitumor activity of cisplatin and toxal on A2780/DDP cells, supress cell-matrix adhesion of A2780/DDP, inhibit the cell proliferation, result in A2780/DDP cells apoptosis. In addition, silibinin could effectively reduce cisplatin and/or toxal-induced hepatotoxicity by protecting DNA from damage and restoring the potential of cell proliferation in cisplatin and/or toxal-treated LO2 cells.Conclusion: Our results suggest that silibinin could restore the sensitivity of cisplatin and taxol in drug-resistant human ovarian cancer cells and reduce durg-induced hepatotoxicity in cell level.Keywords: silibinin, cisplatin and/or taxol, drug resistance, human ovarian cancer, hepatotoxicity

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