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Silibinin restores the sensitivity of cisplatin and taxol in A2780-resistant cell and reduces drug-induced hepatotoxicity
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 silib...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668021/ https://www.ncbi.nlm.nih.gov/pubmed/31440098 http://dx.doi.org/10.2147/CMAR.S201341 |
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author | Yang, Zhichun Pan, Qionghui Zhang, Dingfang Chen, Jianqiang Qiu, Yinda Chen, Xiaojing Zheng, Feiyun Lin, Feng |
author_facet | Yang, Zhichun Pan, Qionghui Zhang, Dingfang Chen, Jianqiang Qiu, Yinda Chen, Xiaojing Zheng, Feiyun Lin, Feng |
author_sort | Yang, Zhichun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6668021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-66680212019-08-22 Silibinin restores the sensitivity of cisplatin and taxol in A2780-resistant cell and reduces drug-induced hepatotoxicity Yang, Zhichun Pan, Qionghui Zhang, Dingfang Chen, Jianqiang Qiu, Yinda Chen, Xiaojing Zheng, Feiyun Lin, Feng Cancer Manag Res Original Research 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. Dove 2019-07-26 /pmc/articles/PMC6668021/ /pubmed/31440098 http://dx.doi.org/10.2147/CMAR.S201341 Text en © 2019 Yang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Yang, Zhichun Pan, Qionghui Zhang, Dingfang Chen, Jianqiang Qiu, Yinda Chen, Xiaojing Zheng, Feiyun Lin, Feng Silibinin restores the sensitivity of cisplatin and taxol in A2780-resistant cell and reduces drug-induced hepatotoxicity |
title | Silibinin restores the sensitivity of cisplatin and taxol in A2780-resistant cell and reduces drug-induced hepatotoxicity |
title_full | Silibinin restores the sensitivity of cisplatin and taxol in A2780-resistant cell and reduces drug-induced hepatotoxicity |
title_fullStr | Silibinin restores the sensitivity of cisplatin and taxol in A2780-resistant cell and reduces drug-induced hepatotoxicity |
title_full_unstemmed | Silibinin restores the sensitivity of cisplatin and taxol in A2780-resistant cell and reduces drug-induced hepatotoxicity |
title_short | Silibinin restores the sensitivity of cisplatin and taxol in A2780-resistant cell and reduces drug-induced hepatotoxicity |
title_sort | silibinin restores the sensitivity of cisplatin and taxol in a2780-resistant cell and reduces drug-induced hepatotoxicity |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668021/ https://www.ncbi.nlm.nih.gov/pubmed/31440098 http://dx.doi.org/10.2147/CMAR.S201341 |
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