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Ivermectin, which is an existing anti\u2010parasitic drug, has been recently identified as a novel anti\u2010cancer drug. In line with previous efforts, this work demonstrates the translational potential of ivermectin to treat advanced HCC. We demonstrated that ivermectin at clinically relevant concentrations was active against growth and survival in multiple HCC cell lines. We showed that ivermectin had the potential to inhibit metastasis and target HCC stem cell functions. Mechanism studies correlated well with cellular phenotypes observed in ivermectin\u2010treated cells, and demonstrated inhibition of mTOR\/STAT3 pathway, suppression of epithelial mesenchymal transition (EMT) and reduced expression of stem cell markers. We further demonstrated that ivermectin inhibited tumor formation and growth in HCC xenograft mouse model, without causing significant toxicity in the mice. Using combination index (CI), we showed that ivermectin and sorafenib were synergistic in HCC in vitro, and this was further confirmed in vivo. Our work demonstrates the potent anti\u2010HCC activities of ivermectin and its multiple targets on essential oncogenic pathways. Our findings provide preclinical evidence to initialize clinical trial using ivermectin and sorafenib for treating advanced HCC.<\/jats:p>","DOI":"10.1002\/prp2.954","type":"journal-article","created":{"date-parts":[[2022,5,15]],"date-time":"2022-05-15T02:50:16Z","timestamp":1652583016000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["RETRACTED: Ivermectin synergizes sorafenib in hepatocellular carcinoma via targeting multiple oncogenic pathways"],"prefix":"10.1002","volume":"10","author":[{"given":"Haofeng","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery The First Affiliated Hospital of Yangtze University  Jingzhou China"},{"name":"Department of Hepatobiliary Surgery Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of 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