Combination of Detoxified Pneumolysin Derivative ΔA146Ply and Berbamine as a Treatment Approach for Breast Cancer
Increasing evidence demonstrates that microorganisms and their products can modulate host responses to cancer therapies and contribute to tumor shrinkage via various mechanisms, including intracellular signaling pathways modulation and immunomodulation. Detoxified pneumolysin derivative ΔA146Ply is...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-09-01
|
| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770520300942 |
| _version_ | 1818291438326120448 |
|---|---|
| author | Hong Zhang Tao Zhu Ruoqiu Fu Yang Peng Peng Jing Wenchun Xu Hong Wang Sijie Li Zhaoche Shu Yibing Yin Xuemei Zhang |
| author_facet | Hong Zhang Tao Zhu Ruoqiu Fu Yang Peng Peng Jing Wenchun Xu Hong Wang Sijie Li Zhaoche Shu Yibing Yin Xuemei Zhang |
| author_sort | Hong Zhang |
| collection | DOAJ |
| description | Increasing evidence demonstrates that microorganisms and their products can modulate host responses to cancer therapies and contribute to tumor shrinkage via various mechanisms, including intracellular signaling pathways modulation and immunomodulation. Detoxified pneumolysin derivative ΔA146Ply is a pneumolysin mutant lacking hemolytic activity. To determine the antitumor activity of ΔA146Ply, the combination of ΔA146Ply and berbamine, a well-established antitumor agent, was used for breast cancer therapy, especially for triple-negative breast cancer. The efficacy of the combination therapy was evaluated in vitro using four breast cancer cell lines and in vivo using a synergistic mouse tumor model. We demonstrated that in vitro, the combination therapy significantly inhibited cancer cell proliferation, promoted cancer cell apoptosis, caused cancer cell-cycle arrest, and suppressed cancer cell migration and invasion. In vivo, the combination therapy significantly suppressed tumor growth and prolonged the median survival time of tumor-bearing mice partially through inhibiting tumor cell proliferation, promoting tumor cell apoptosis, and activating systemic antitumor immune responses. The safety analysis demonstrated that the combination therapy showed no obvious liver and kidney toxicity to tumor-bearing mice. Our study provides a new treatment option for breast cancer and lays the experimental basis for the development of ΔA146Ply as an antitumor agent. |
| first_indexed | 2024-12-13T02:44:04Z |
| format | Article |
| id | doaj.art-4188023051db40c2a2b651e83fa20939 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-12-13T02:44:04Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-4188023051db40c2a2b651e83fa209392022-12-22T00:02:13ZengElsevierMolecular Therapy: Oncolytics2372-77052020-09-0118247261Combination of Detoxified Pneumolysin Derivative ΔA146Ply and Berbamine as a Treatment Approach for Breast CancerHong Zhang0Tao Zhu1Ruoqiu Fu2Yang Peng3Peng Jing4Wenchun Xu5Hong Wang6Sijie Li7Zhaoche Shu8Yibing Yin9Xuemei Zhang10Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, China; Department of Laboratory Medicine, The Affiliated Hospital of North Sichuan Medical College and Department of Laboratory Medicine and Translational Medicine Research Center, North Sichuan Medical College, Nanchong 637000, ChinaDepartment of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, ChinaDepartment of Pharmacy, Daping Hospital, Army Medical University, Chongqing 400042, ChinaDepartment of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, ChinaDepartment of Pediatric Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, ChinaDepartment of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, ChinaDepartment of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, ChinaDepartment of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, ChinaDepartment of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, ChinaDepartment of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, ChinaDepartment of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, China; Corresponding author: Xuemei Zhang, Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, People’s Republic of China.Increasing evidence demonstrates that microorganisms and their products can modulate host responses to cancer therapies and contribute to tumor shrinkage via various mechanisms, including intracellular signaling pathways modulation and immunomodulation. Detoxified pneumolysin derivative ΔA146Ply is a pneumolysin mutant lacking hemolytic activity. To determine the antitumor activity of ΔA146Ply, the combination of ΔA146Ply and berbamine, a well-established antitumor agent, was used for breast cancer therapy, especially for triple-negative breast cancer. The efficacy of the combination therapy was evaluated in vitro using four breast cancer cell lines and in vivo using a synergistic mouse tumor model. We demonstrated that in vitro, the combination therapy significantly inhibited cancer cell proliferation, promoted cancer cell apoptosis, caused cancer cell-cycle arrest, and suppressed cancer cell migration and invasion. In vivo, the combination therapy significantly suppressed tumor growth and prolonged the median survival time of tumor-bearing mice partially through inhibiting tumor cell proliferation, promoting tumor cell apoptosis, and activating systemic antitumor immune responses. The safety analysis demonstrated that the combination therapy showed no obvious liver and kidney toxicity to tumor-bearing mice. Our study provides a new treatment option for breast cancer and lays the experimental basis for the development of ΔA146Ply as an antitumor agent.http://www.sciencedirect.com/science/article/pii/S2372770520300942ΔA146PlyBBMtriple-negative breast cancerantitumor agentcombination therapy |
| spellingShingle | Hong Zhang Tao Zhu Ruoqiu Fu Yang Peng Peng Jing Wenchun Xu Hong Wang Sijie Li Zhaoche Shu Yibing Yin Xuemei Zhang Combination of Detoxified Pneumolysin Derivative ΔA146Ply and Berbamine as a Treatment Approach for Breast Cancer Molecular Therapy: Oncolytics ΔA146Ply BBM triple-negative breast cancer antitumor agent combination therapy |
| title | Combination of Detoxified Pneumolysin Derivative ΔA146Ply and Berbamine as a Treatment Approach for Breast Cancer |
| title_full | Combination of Detoxified Pneumolysin Derivative ΔA146Ply and Berbamine as a Treatment Approach for Breast Cancer |
| title_fullStr | Combination of Detoxified Pneumolysin Derivative ΔA146Ply and Berbamine as a Treatment Approach for Breast Cancer |
| title_full_unstemmed | Combination of Detoxified Pneumolysin Derivative ΔA146Ply and Berbamine as a Treatment Approach for Breast Cancer |
| title_short | Combination of Detoxified Pneumolysin Derivative ΔA146Ply and Berbamine as a Treatment Approach for Breast Cancer |
| title_sort | combination of detoxified pneumolysin derivative δa146ply and berbamine as a treatment approach for breast cancer |
| topic | ΔA146Ply BBM triple-negative breast cancer antitumor agent combination therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2372770520300942 |
| work_keys_str_mv | AT hongzhang combinationofdetoxifiedpneumolysinderivativeda146plyandberbamineasatreatmentapproachforbreastcancer AT taozhu combinationofdetoxifiedpneumolysinderivativeda146plyandberbamineasatreatmentapproachforbreastcancer AT ruoqiufu combinationofdetoxifiedpneumolysinderivativeda146plyandberbamineasatreatmentapproachforbreastcancer AT yangpeng combinationofdetoxifiedpneumolysinderivativeda146plyandberbamineasatreatmentapproachforbreastcancer AT pengjing combinationofdetoxifiedpneumolysinderivativeda146plyandberbamineasatreatmentapproachforbreastcancer AT wenchunxu combinationofdetoxifiedpneumolysinderivativeda146plyandberbamineasatreatmentapproachforbreastcancer AT hongwang combinationofdetoxifiedpneumolysinderivativeda146plyandberbamineasatreatmentapproachforbreastcancer AT sijieli combinationofdetoxifiedpneumolysinderivativeda146plyandberbamineasatreatmentapproachforbreastcancer AT zhaocheshu combinationofdetoxifiedpneumolysinderivativeda146plyandberbamineasatreatmentapproachforbreastcancer AT yibingyin combinationofdetoxifiedpneumolysinderivativeda146plyandberbamineasatreatmentapproachforbreastcancer AT xuemeizhang combinationofdetoxifiedpneumolysinderivativeda146plyandberbamineasatreatmentapproachforbreastcancer |