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Clarithromycin synergizes with cisplatin to inhibit ovarian cancer growth in vitro and in vivo

BACKGROUND: Cisplatin-based chemotherapy is the first-line treatment for ovarian cancer. However, acquired resistance to cisplatin treatment often occurs in epithelial ovarian cancer, and effective and practical methods for overcoming this obstacle are urgently needed. The study aimed to demonstrate...

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Autores principales: Zhou, Bo, Xia, Meng, Wang, Bin, Thapa, Niresh, Gan, Lijuan, Sun, Chaoyang, Guo, Ensong, Huang, Jia, Lu, Yulan, Cai, Hongbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839134/
https://www.ncbi.nlm.nih.gov/pubmed/31703731
http://dx.doi.org/10.1186/s13048-019-0570-9
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author Zhou, Bo
Xia, Meng
Wang, Bin
Thapa, Niresh
Gan, Lijuan
Sun, Chaoyang
Guo, Ensong
Huang, Jia
Lu, Yulan
Cai, Hongbin
author_facet Zhou, Bo
Xia, Meng
Wang, Bin
Thapa, Niresh
Gan, Lijuan
Sun, Chaoyang
Guo, Ensong
Huang, Jia
Lu, Yulan
Cai, Hongbin
author_sort Zhou, Bo
collection PubMed
description BACKGROUND: Cisplatin-based chemotherapy is the first-line treatment for ovarian cancer. However, acquired resistance to cisplatin treatment often occurs in epithelial ovarian cancer, and effective and practical methods for overcoming this obstacle are urgently needed. The study aimed to demonstrate the synergistic effect of clarithromycin (CAM) with cisplatin to inhibit ovarian carcinoma cells growth in vitro and in vivo. RESULTS: We performed CCK-8 assay to detect apoptosis rates in response to CAM alone or in combination with cisplatin, which were further confirmed by Annexin V and PI staining methods and western blotting. Mechanistically, CAM could reduce endogenous antioxidant enzyme expression and increase the levels of reactive oxygen species (ROS) to augment the cytotoxic effect of cisplatin. Meanwhile, a tumor xenograft model in athymic BALB/c-nude mice demonstrated that CAM combined with cisplatin resulted in reduced tumor growth and weight compared with cisplatin alone. CONCLUSION: Collectively, our results indicate that CAM works synergistically with cisplatin to inhibit ovarian cancer cell growth, which may be manipulated by a ROS-mediated mechanism that enhances cisplatin therapy, and offers a novel strategy for overcoming cisplatin therapy resistance.
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spelling pubmed-68391342019-11-12 Clarithromycin synergizes with cisplatin to inhibit ovarian cancer growth in vitro and in vivo Zhou, Bo Xia, Meng Wang, Bin Thapa, Niresh Gan, Lijuan Sun, Chaoyang Guo, Ensong Huang, Jia Lu, Yulan Cai, Hongbin J Ovarian Res Research BACKGROUND: Cisplatin-based chemotherapy is the first-line treatment for ovarian cancer. However, acquired resistance to cisplatin treatment often occurs in epithelial ovarian cancer, and effective and practical methods for overcoming this obstacle are urgently needed. The study aimed to demonstrate the synergistic effect of clarithromycin (CAM) with cisplatin to inhibit ovarian carcinoma cells growth in vitro and in vivo. RESULTS: We performed CCK-8 assay to detect apoptosis rates in response to CAM alone or in combination with cisplatin, which were further confirmed by Annexin V and PI staining methods and western blotting. Mechanistically, CAM could reduce endogenous antioxidant enzyme expression and increase the levels of reactive oxygen species (ROS) to augment the cytotoxic effect of cisplatin. Meanwhile, a tumor xenograft model in athymic BALB/c-nude mice demonstrated that CAM combined with cisplatin resulted in reduced tumor growth and weight compared with cisplatin alone. CONCLUSION: Collectively, our results indicate that CAM works synergistically with cisplatin to inhibit ovarian cancer cell growth, which may be manipulated by a ROS-mediated mechanism that enhances cisplatin therapy, and offers a novel strategy for overcoming cisplatin therapy resistance. BioMed Central 2019-11-08 /pmc/articles/PMC6839134/ /pubmed/31703731 http://dx.doi.org/10.1186/s13048-019-0570-9 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zhou, Bo
Xia, Meng
Wang, Bin
Thapa, Niresh
Gan, Lijuan
Sun, Chaoyang
Guo, Ensong
Huang, Jia
Lu, Yulan
Cai, Hongbin
Clarithromycin synergizes with cisplatin to inhibit ovarian cancer growth in vitro and in vivo
title Clarithromycin synergizes with cisplatin to inhibit ovarian cancer growth in vitro and in vivo
title_full Clarithromycin synergizes with cisplatin to inhibit ovarian cancer growth in vitro and in vivo
title_fullStr Clarithromycin synergizes with cisplatin to inhibit ovarian cancer growth in vitro and in vivo
title_full_unstemmed Clarithromycin synergizes with cisplatin to inhibit ovarian cancer growth in vitro and in vivo
title_short Clarithromycin synergizes with cisplatin to inhibit ovarian cancer growth in vitro and in vivo
title_sort clarithromycin synergizes with cisplatin to inhibit ovarian cancer growth in vitro and in vivo
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839134/
https://www.ncbi.nlm.nih.gov/pubmed/31703731
http://dx.doi.org/10.1186/s13048-019-0570-9
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