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Doramectin (DOR), a third-generation derivative of avermectins (AVMs), is renowned for its low toxicity and high efficiency. However, no research has hitherto focused on the anti-cholangiocarcinoma effects of these drugs. In this study, we undertook a preliminary exploration of the mechanism through which DOR inhibits the viability of human cholangiocarcinoma cells (Mz-ChA-1) via transcriptome analysis and molecular validation at the cellular level. The results indicated that DOR could suppress the growth and proliferation of Mz-ChA-1 cells in a dose-dependent manner. Moreover, it significantly diminished their migration and invasion abilities. Cell cycle analysis disclosed arrest in the G1 phase, accompanied by an increase in p21 expression and a decrease in the levels of the cyclin E1 and CDK2 proteins. Additionally, DOR induced apoptosis via the ROS-triggered mitochondrial pathway. This was attested by an elevation in the BAX\/BCL-2 ratio, the activation of caspase 3\/7 and the cleavage of PARP1. These mechanistic insights underscore DOR\u2019s potential as a therapeutic agent against cholangiocarcinoma<\/jats:p>","DOI":"10.3390\/ijms252413440","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T04:14:52Z","timestamp":1734322492000},"page":"13440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Apoptosis-Inducing and Proliferation-Inhibiting Effects of Doramectin on Mz-ChA-1 Human Cholangiocarcinoma Cells"],"prefix":"10.3390","volume":"25","author":[{"given":"Yunfang","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5838-5238","authenticated-orcid":false,"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3951-8873","authenticated-orcid":false,"given":"Yan","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehong","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Dai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Ke","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhu","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5688-929X","authenticated-orcid":false,"given":"Mingliang","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"},{"name":"Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Ocean University, Lianyungang 222000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4815-3260","authenticated-orcid":false,"given":"Qin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"607","DOI":"10.4251\/wjgo.v14.i3.607","article-title":"Pathological, molecular, and clinical characteristics of cholangiocarcinoma: A comprehensive review","volume":"14","author":"Vij","year":"2022","journal-title":"World J. 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