{"data":{"id":"10.6084/m9.figshare.1623206","type":"dois","attributes":{"doi":"10.6084/m9.figshare.1623206","prefix":"10.6084","suffix":"m9.figshare.1623206","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Li, Jin","givenName":"Jin","familyName":"Li","affiliation":[],"nameIdentifiers":[]},{"name":"Li, Bin","givenName":"Bin","familyName":"Li","affiliation":[],"nameIdentifiers":[]},{"name":"Wah Chan, Kwok","givenName":"Kwok","familyName":"Wah Chan","affiliation":[],"nameIdentifiers":[]},{"name":"Law, Simon","givenName":"Simon","familyName":"Law","affiliation":[],"nameIdentifiers":[]},{"name":"Wah Tsao, Sai","givenName":"Sai","familyName":"Wah Tsao","affiliation":[],"nameIdentifiers":[]},{"name":"Wen Xu, Wen","givenName":"Wen","familyName":"Wen Xu","affiliation":[],"nameIdentifiers":[]},{"name":"Yuan Guan, Xin","givenName":"Xin","familyName":"Yuan Guan","affiliation":[],"nameIdentifiers":[]},{"name":"Ru Qin, Yan","givenName":"Yan","familyName":"Ru Qin","affiliation":[],"nameIdentifiers":[]},{"name":"Pui Yue Lee, Nikki","givenName":"Nikki","familyName":"Pui Yue Lee","affiliation":[],"nameIdentifiers":[]},{"name":"Tak Chan, Kin","givenName":"Kin","familyName":"Tak Chan","affiliation":[],"nameIdentifiers":[]},{"name":"LM Cheung, Annie","givenName":"Annie","familyName":"LM Cheung","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Role of AMPK signaling in mediating the anticancer effects of silibinin in esophageal squamous cell carcinoma"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Hematology"},{"subject":"Cancer"},{"subject":"Developmental Biology"},{"subject":"Biological Sciences"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Chemistry"},{"subject":"Biotechnology"},{"subject":"Pharmacology"},{"subject":"Cell Biology"},{"subject":"Biochemistry"}],"contributors":[],"dates":[{"date":"2015-12-17","dateType":"Created"},{"date":"2023-06-01","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1517/14728222.2016.1121236","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["5317072 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"\u003cb\u003e\u003ci\u003eObjective\u003c/i\u003e\u003c/b\u003e: Emerging evidence suggests that activation of adenosine monophosphate-activated protein kinase (AMPK) may suppress cancer growth. Identification of novel AMPK activators is therefore crucial to exploit AMPK as a potential target for cancer prevention and treatment.\u003cb\u003e\u003ci\u003eResearch design and methods\u003c/i\u003e\u003c/b\u003e: We determined the expression status and role of AMPK in esophageal squamous cell carcinoma (ESCC) and investigated whether silibinin, a nontoxic natural product, could activate AMPK to inhibit ESCC development.\u003cb\u003e\u003ci\u003eResults\u003c/i\u003e\u003c/b\u003e: Our results from 49 pairs of human ESCC and normal tissues showed that AMPK was constitutively inactive in the majority (69.4%) of ESCC. We found that silibinin induced apoptosis, and inhibited ESCC cell proliferation \u003ci\u003ein vitro\u003c/i\u003e and tumorigenicity \u003ci\u003ein vivo\u003c/i\u003e without any adverse effects. Silibinin also markedly suppressed the invasive potential of ESCC cells \u003ci\u003ein vitro\u003c/i\u003e and their ability to form lung metastasis in nude mice. The anticancer effects of silibinin were abrogated by the presence of compound C or shRNA against AMPK. More importantly, silibinin enhanced the sensitivity of ESCC cells and tumors to the chemotherapeutic drugs, 5-fluorouracil and cisplatin.\u003cb\u003e\u003ci\u003eConclusions\u003c/i\u003e\u003c/b\u003e: This preclinical study supports that AMPK is a valid therapeutic target and suggests that silibinin may be a potentially useful therapeutic agent and chemosensitizer for esophageal cancer.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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