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

Abstract

PURPOSE:

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.

• Authors: Zhichun Yang, Qionghui Pan, Dingfang Zhang, Jianqiang Chen, Yinda Qiu, Xiaojing Chen, Feiyun Zheng, Feng Lin
• Journal: Cancer management and research (Cancer Manag Res) Vol. 11 Pg. 7111-7122 ( 2019) ISSN: 1179-1322 [Print] New Zealand
• PMID: 31440098 (Publication Type: Journal Article)