1. Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway
- Author
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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, and Dengke Bao
- Subjects
Cancer Research ,Esophageal Neoplasms ,Mice, Nude ,Antineoplastic Agents ,Apoptosis ,NF-κB ,Mice ,Cell Line, Tumor ,parasitic diseases ,Genetics ,Animals ,Humans ,RC254-282 ,Cell Proliferation ,Membrane Potential, Mitochondrial ,Ivermectin ,Research ,ESCC ,NF-kappa B ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,digestive system diseases ,Mitochondria ,Mitochondrial ,Disease Models, Animal ,Oncology ,Esophageal Squamous Cell Carcinoma ,Reactive Oxygen Species ,Signal Transduction - 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.
- Published
- 2021