Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway

BMC Cancer - 2021
Nana Xu1, Mengmeng Lu1, Jiaxin Wang1, Yujia Li1, Xiaotian Yang1, Xiajie Wei1, Jiaoyang Si1, Jingru Han1, Xiaojuan Yao1, Juanmei Zhang1, Junqi Liu2, Yanming Liu3, Hushan Yang4, Dan Bao1
1Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Huaihe Hospital, Henan University, Kaifeng, 475004, Henan, China
2Department of Radiation Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
3Department of Cardiology, Huaihe Hospital, Henan University, Kaifeng, 475000, Henan, China
4Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA

Tóm tắt

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.

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