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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Format: | Article |
Language: | English |
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BMC
2019-11-01
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Series: | Journal of Ovarian Research |
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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. |
first_indexed | 2024-04-11T02:22:43Z |
format | Article |
id | doaj.art-7a5d8ca1500c4dcb8419bd9340942947 |
institution | Directory Open Access Journal |
issn | 1757-2215 |
language | English |
last_indexed | 2024-04-11T02:22:43Z |
publishDate | 2019-11-01 |
publisher | BMC |
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series | Journal of Ovarian Research |
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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