{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:03:30Z","timestamp":1762542210948,"version":"3.37.3"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,7,16]],"date-time":"2013-07-16T00:00:00Z","timestamp":1373932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["30900237","30772583"],"award-info":[{"award-number":["30900237","30772583"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"crossref","award":["2009CB521807"],"award-info":[{"award-number":["2009CB521807"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National S&T Major Special Project on Major New Drug Innovation","award":["2009ZX09301-003"],"award-info":[{"award-number":["2009ZX09301-003"]}]},{"name":"Fundamental Research Funds for Central Universities","award":["XDJK2010C059"],"award-info":[{"award-number":["XDJK2010C059"]}]},{"name":"Southwest University Doctor Foundation","award":["SWU112102"],"award-info":[{"award-number":["SWU112102"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Recently, tumor initiating cells are considered as the central role of tumorigenicity in hepatocellular carcinoma. Enediyne anticancer antibiotic lidamycin with great potential antitumor activity is currently evaluated in Phase II clinical trials. In this study, we evaluated the effect of lidamycin on tumor initiating cells of hepatocellular carcinoma Huh7 and identified the potential mechanism. Flow cytometry analysis and sorting assay, surface marker assay, sphere formation assay, and aldefluor assay were used to evaluate the effect of lidamycin on Huh7 tumor initiating cells in vitro. To investigate the potential mechanism, the activity of GSK3\u03b2\/\u03b2\u2010catenin pathway was detected by Western blot and T cell factors transcriptional activity assay. Subcutaneous tumor model in nude mice was used to observe in vivo effect of lidamycin on Huh7 cells. Lidamycin decreased the proportion of EpCAM<jats:sup>+<\/jats:sup> cells and the expression of EpCAM protein. Lidamycin inhibited sphere formation of sorted EpCAM<jats:sup>+<\/jats:sup> cells in 7 d, and of parental cells in three serial passages. The population of aldehyde dehydrogenase\u2010positive cells was reduced by lidamycin. In addition, lidamycin restrained tumor volume and incidence in vivo. Lidamycin activated GSK3\u03b2, and degraded the activity of \u03b2\u2010catenin. Consequently, transcriptional activity of \u03b2\u2010catenin\/T cell factors was decreased. In brief, these results suggest that lidamycin suppressed Huh7 tumor initiating cells via GSK3\u03b2\/\u03b2\u2010catenin pathway. These findings reveal the potential mechanism of lidamycin on tumor initiating cells and the benefit for further clinical evaluation. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22069","type":"journal-article","created":{"date-parts":[[2013,7,16]],"date-time":"2013-07-16T08:48:46Z","timestamp":1373964526000},"page":"1-8","source":"Crossref","is-referenced-by-count":13,"title":["Lidamycin inhibits tumor initiating cells of hepatocellular carcinoma Huh7 through GSK3\u03b2\/\u03b2\u2010catenin pathway"],"prefix":"10.1002","volume":"54","author":[{"given":"Yi","family":"Chen","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Sciences Southwest University Chongqing China"},{"name":"Laboratory of Oncology MOH Key Laboratory of Antibiotic Bioengineering Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 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