{"data":{"id":"10.6084/m9.figshare.c.2166857.v1","type":"dois","attributes":{"doi":"10.6084/m9.figshare.c.2166857.v1","prefix":"10.6084","suffix":"m9.figshare.c.2166857.v1","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":"2019-08-19","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[{"relationType":"IsIdenticalTo","relatedIdentifier":"10.6084/m9.figshare.c.2166857","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":[],"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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