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

Abstract 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 dem...

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Main Authors: Bo Zhou, Meng Xia, Bin Wang, Niresh Thapa, Lijuan Gan, Chaoyang Sun, Ensong Guo, Jia Huang, Yulan Lu, Hongbin Cai
Format: Article
Language:English
Published: BMC 2019-11-01
Series:Journal of Ovarian Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13048-019-0570-9
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author Bo Zhou
Meng Xia
Bin Wang
Niresh Thapa
Lijuan Gan
Chaoyang Sun
Ensong Guo
Jia Huang
Yulan Lu
Hongbin Cai
author_facet Bo Zhou
Meng Xia
Bin Wang
Niresh Thapa
Lijuan Gan
Chaoyang Sun
Ensong Guo
Jia Huang
Yulan Lu
Hongbin Cai
author_sort Bo Zhou
collection DOAJ
description Abstract 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 doaj.art-7a5d8ca1500c4dcb8419bd93409429472023-01-02T23:19:02ZengBMCJournal of Ovarian Research1757-22152019-11-0112111010.1186/s13048-019-0570-9Clarithromycin synergizes with cisplatin to inhibit ovarian cancer growth in vitro and in vivoBo Zhou0Meng Xia1Bin Wang2Niresh Thapa3Lijuan Gan4Chaoyang Sun5Ensong Guo6Jia Huang7Yulan Lu8Hongbin Cai9Department of Gynecologic Oncology, Zhongnan Hospital of Wuhan UniversityCancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyHubei Provincial Institute for Food Supervision and TestDepartment of Gynecologic Oncology, Zhongnan Hospital of Wuhan UniversityDepartment of Gynecologic Oncology, Zhongnan Hospital of Wuhan UniversityCancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gynecologic Oncology, Zhongnan Hospital of Wuhan UniversityDepartment of Gynecologic Oncology, Zhongnan Hospital of Wuhan UniversityAbstract 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.http://link.springer.com/article/10.1186/s13048-019-0570-9Ovarian cancerClarithromycinCisplatin-resistanceCombination therapy
spellingShingle Bo Zhou
Meng Xia
Bin Wang
Niresh Thapa
Lijuan Gan
Chaoyang Sun
Ensong Guo
Jia Huang
Yulan Lu
Hongbin Cai
Clarithromycin synergizes with cisplatin to inhibit ovarian cancer growth in vitro and in vivo
Journal of Ovarian Research
Ovarian cancer
Clarithromycin
Cisplatin-resistance
Combination therapy
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 Ovarian cancer
Clarithromycin
Cisplatin-resistance
Combination therapy
url http://link.springer.com/article/10.1186/s13048-019-0570-9
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