Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway
Abstract Background Esophageal squamous cell carcinoma (ESCC) is the most predominant primary malignant tumor among worldwide, especially in China. To date, the successful treatment remains a mainly clinical challenge, it is imperative to develop successful therapeutic agents. Methods The anti-proli...
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| Format: | Article |
| Language: | English |
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BMC
2021-12-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-021-09021-x |
| _version_ | 1818461598469062656 |
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| author | Nana Xu Mengmeng Lu Jiaxin Wang Yujia Li Xiaotian Yang Xiajie Wei Jiaoyang Si Jingru Han Xiaojuan Yao Juanmei Zhang Junqi Liu Yanming Li Hushan Yang Dengke Bao |
| author_facet | Nana Xu Mengmeng Lu Jiaxin Wang Yujia Li Xiaotian Yang Xiajie Wei Jiaoyang Si Jingru Han Xiaojuan Yao Juanmei Zhang Junqi Liu Yanming Li Hushan Yang Dengke Bao |
| author_sort | Nana Xu |
| collection | DOAJ |
| description | Abstract Background Esophageal squamous cell carcinoma (ESCC) is the most predominant primary malignant tumor among worldwide, especially in China. To date, the successful treatment remains a mainly clinical challenge, it is imperative to develop successful therapeutic agents. Methods The anti-proliferative effect of ivermectin on ESCC is investigated in cell model and in nude mice model. Cell apoptosis was assessed using flow cytometry, TUNEL assay and western blotting. Mitochondrial dysfunction was determined by reactive oxygen species accumulation, mitochondrial membrane potential and ATP levels. Results Our results determined that ivermectin significantly inhibited the proliferation of ESCC cells in vitro and in vivo. Furthermore, we found that ivermectin markedly mediated mitochondrial dysfunction and induced apoptosis of ESCC cells, which indicated the anti-proliferative effect of ivermectin on ESCC cells was implicated in mitochondrial apoptotic pathway. Mechanistically, ivermectin significantly triggered ROS accumulation and inhibited the activation of NF-κB signaling pathway and increased the ratio of Bax/Bcl-2. Conclusions These finding indicated that ivermectin has significant anti-tumour potential for ESSC and may be a potential therapeutic candidate against ESCC. |
| first_indexed | 2024-12-14T23:48:41Z |
| format | Article |
| id | doaj.art-dece482ee73a431e936f008dba73d37f |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-14T23:48:41Z |
| publishDate | 2021-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-dece482ee73a431e936f008dba73d37f2022-12-21T22:43:19ZengBMCBMC Cancer1471-24072021-12-0121111110.1186/s12885-021-09021-xIvermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathwayNana Xu0Mengmeng Lu1Jiaxin Wang2Yujia Li3Xiaotian Yang4Xiajie Wei5Jiaoyang Si6Jingru Han7Xiaojuan Yao8Juanmei Zhang9Junqi Liu10Yanming Li11Hushan Yang12Dengke Bao13Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Huaihe Hospital, Henan UniversityLaboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Huaihe Hospital, Henan UniversityLaboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Huaihe Hospital, Henan UniversityLaboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Huaihe Hospital, Henan UniversityLaboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Huaihe Hospital, Henan UniversityLaboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Huaihe Hospital, Henan UniversityLaboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Huaihe Hospital, Henan UniversityLaboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Huaihe Hospital, Henan UniversityLaboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Huaihe Hospital, Henan UniversityLaboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Huaihe Hospital, Henan UniversityDepartment of Radiation Oncology, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Cardiology, Huaihe Hospital, Henan UniversityDepartment of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson UniversityLaboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Huaihe Hospital, Henan UniversityAbstract Background Esophageal squamous cell carcinoma (ESCC) is the most predominant primary malignant tumor among worldwide, especially in China. To date, the successful treatment remains a mainly clinical challenge, it is imperative to develop successful therapeutic agents. Methods The anti-proliferative effect of ivermectin on ESCC is investigated in cell model and in nude mice model. Cell apoptosis was assessed using flow cytometry, TUNEL assay and western blotting. Mitochondrial dysfunction was determined by reactive oxygen species accumulation, mitochondrial membrane potential and ATP levels. Results Our results determined that ivermectin significantly inhibited the proliferation of ESCC cells in vitro and in vivo. Furthermore, we found that ivermectin markedly mediated mitochondrial dysfunction and induced apoptosis of ESCC cells, which indicated the anti-proliferative effect of ivermectin on ESCC cells was implicated in mitochondrial apoptotic pathway. Mechanistically, ivermectin significantly triggered ROS accumulation and inhibited the activation of NF-κB signaling pathway and increased the ratio of Bax/Bcl-2. Conclusions These finding indicated that ivermectin has significant anti-tumour potential for ESSC and may be a potential therapeutic candidate against ESCC.https://doi.org/10.1186/s12885-021-09021-xESCCIvermectinApoptosisMitochondrialNF-κB |
| spellingShingle | Nana Xu Mengmeng Lu Jiaxin Wang Yujia Li Xiaotian Yang Xiajie Wei Jiaoyang Si Jingru Han Xiaojuan Yao Juanmei Zhang Junqi Liu Yanming Li Hushan Yang Dengke Bao Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway BMC Cancer ESCC Ivermectin Apoptosis Mitochondrial NF-κB |
| title | Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway |
| title_full | Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway |
| title_fullStr | Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway |
| title_full_unstemmed | Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway |
| title_short | Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway |
| title_sort | ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway |
| topic | ESCC Ivermectin Apoptosis Mitochondrial NF-κB |
| url | https://doi.org/10.1186/s12885-021-09021-x |
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