简介：结直肠癌（CRC）是全球第四常见的癌症，其发病率和死亡率高。近年来，高脂饮食被证明可以增加CRC发病率，标志着降脂药物在CRC治疗中的应用可能性。本研究初步评估了依泽替米在通过阻止小肠内的脂质吸收对抗CRC的效果和机制。 方法：本研究使用细胞和分子技术评估了CRC细胞增殖、侵袭、凋亡和自噬。荧光显微镜和流式细胞术被用于评估体外线粒体活力。皮下异种移植小鼠模型被用于评估依泽替米对体内的影响。 结果：我们发现依泽替米抑制了HCT116和Caco2细胞的增殖和迁移，并促进了与自噬相关的凋亡。发现依泽替米诱导的CRC细胞线粒体功能障碍与mTOR信号通路活性相关。 讨论：依泽替米通过促进mTOR信号依赖的线粒体功能障碍促进了对抗CRC的效果，突显了其在CRC治疗中的潜在价值。版权所有©2023 Zheng，Yang，Jia，Ji，Wu，Feng，Li，Cheng，Zhang，Li，Dai，Xu，Wu，Zhou和Guo。

Introduction: Colorectal cancer (CRC) is the fourth most common cancer worldwide, with high morbidity and mortality rates. In recent years, high-fat diet has been shown to increase CRC morbidity, highlighting the possibility of the application of hypolipidemic drugs for CRC treatment. In this study, we preliminarily evaluated the effects and mechnisms of ezetimibe against CRC through the blockage of lipid absorption in small intesine. Methods: In this study, CRC cell proliferation, invasion, apoptosis, and autophagy were evaluated using cellular and molecular assays. Fluorescent microscopy, and a flow cytometric assay were used to assess mitochondrial activity in vitro. A subcutaneous xenograft mouse model was used to evaluate the effects of ezetimibe in vivo. Results: We found that ezetimibe inhibited CRC cell proliferation, and migration, and facilitated autophage-associated apoptosis in HCT116 and Caco2 cells. Ezetimibe-induced mitochondrial dysfunction in CRC cells was found to be correlated with mTOR signaling activity. Discussion: Ezetimibe exhibits effects against CRC through the promotion of cancer cell death via mTOR signaling-dependent mitochondrial dysfunction, highlighting its potential value in CRC therapy.Copyright © 2023 Zheng, Yang, Jia, Ji, Wu, Feng, Li, Cheng, Zhang, Li, Dai, Xu, Wu, Zhou and Guo.