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Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway

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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. | Xu et al. BMC Cancer 2021 21 1307 https doi.org 10.1186 s12885-021-09021-x RESEARCH Open Access Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway Nana Xu1 Mengmeng Lu1 Jiaxin Wang1 Yujia Li1 Xiaotian Yang1 Xiajie Wei1 Jiaoyang Si1 Jingru Han1 Xiaojuan Yao1 Juanmei Zhang1 Junqi Liu2 Yanming Li3 Hushan Yang4 and Dengke Bao1 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. Keywords ESCC Ivermectin Apoptosis Mitochondrial NF-κB Background to its poor prognosis and high mortality rate with a Esophageal squamous cell carcinoma ESCC is one 5-year survival rate of only about 20 3 5 . Since most of the most common and fatal malignancies in China patients diagnosed with ESCC were found to have locally 1 2 which is .