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Article: Suppression of esophageal tumor growth and chemoresistance by directly targeting the PI3K/AKT pathway

TitleSuppression of esophageal tumor growth and chemoresistance by directly targeting the PI3K/AKT pathway
Authors
Issue Date2014
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html
Citation
Oncotarget, 2014, v. 5 n. 22, p. 11576-11587 How to Cite?
AbstractEsophageal cancer is the sixth most common cause of cancer-related deaths worldwide. Novel therapeutic intervention is urgently needed for this deadly disease. The functional role of PI3K/AKT pathway in esophageal cancer is little known. In this study, our results from 49 pairs of human esophageal tumor and normal specimens demonstrated that AKT was constitutively active in the majority (75.5%) of esophageal tumors compared with corresponding normal tissues. Inhibition of the PI3K/AKT pathway with specific inhibitors, wortmannin and LY294002, significantly reduced Bcl-xL expression, induced caspase-3-dependent apoptosis, and repressed cell proliferation and tumor growth in vitro and in vivo without obvious toxic effects. Moreover, significantly higher expression level of p-AKT was observed in fluorouracil (5-FU)-resistant esophageal cancer cells. Inactivation of PI3K/AKT pathway markedly increased the sensitivity and even reversed acquired resistance of esophageal cancer cells to chemotherapeutic drugs in vitro. More importantly, the resistance of tumor xenografts derived from esophageal cancer cells with acquired 5-FU resistance to chemotherapeutic drugs was significantly abrogated by wortmannin treatment in animals. In summary, our data support PI3K/AKT as a valid therapeutic target and strongly suggest that PI3K/AKT inhibitors used in conjunction with conventional chemotherapy may be a potentially useful therapeutic strategy in treating esophageal cancer patients.
Persistent Identifierhttp://hdl.handle.net/10722/207709
ISSN
2015 Impact Factor: 5.008
2015 SCImago Journal Rankings: 2.294
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, B-
dc.contributor.authorLi, J-
dc.contributor.authorXu, WW-
dc.contributor.authorGuan, XY-
dc.contributor.authorQin, YR-
dc.contributor.authorZhang, LY-
dc.contributor.authorLaw, SYK-
dc.contributor.authorTsao, GSW-
dc.contributor.authorCheung, ALM-
dc.date.accessioned2015-01-19T09:11:20Z-
dc.date.available2015-01-19T09:11:20Z-
dc.date.issued2014-
dc.identifier.citationOncotarget, 2014, v. 5 n. 22, p. 11576-11587-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/10722/207709-
dc.description.abstractEsophageal cancer is the sixth most common cause of cancer-related deaths worldwide. Novel therapeutic intervention is urgently needed for this deadly disease. The functional role of PI3K/AKT pathway in esophageal cancer is little known. In this study, our results from 49 pairs of human esophageal tumor and normal specimens demonstrated that AKT was constitutively active in the majority (75.5%) of esophageal tumors compared with corresponding normal tissues. Inhibition of the PI3K/AKT pathway with specific inhibitors, wortmannin and LY294002, significantly reduced Bcl-xL expression, induced caspase-3-dependent apoptosis, and repressed cell proliferation and tumor growth in vitro and in vivo without obvious toxic effects. Moreover, significantly higher expression level of p-AKT was observed in fluorouracil (5-FU)-resistant esophageal cancer cells. Inactivation of PI3K/AKT pathway markedly increased the sensitivity and even reversed acquired resistance of esophageal cancer cells to chemotherapeutic drugs in vitro. More importantly, the resistance of tumor xenografts derived from esophageal cancer cells with acquired 5-FU resistance to chemotherapeutic drugs was significantly abrogated by wortmannin treatment in animals. In summary, our data support PI3K/AKT as a valid therapeutic target and strongly suggest that PI3K/AKT inhibitors used in conjunction with conventional chemotherapy may be a potentially useful therapeutic strategy in treating esophageal cancer patients.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html-
dc.relation.ispartofOncotarget-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleSuppression of esophageal tumor growth and chemoresistance by directly targeting the PI3K/AKT pathway-
dc.typeArticle-
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hk-
dc.identifier.emailZhang, LY: lyzang@hku.hk-
dc.identifier.emailLaw, SYK: slaw@hku.hk-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.emailCheung, ALM: lmcheung@hku.hk-
dc.identifier.authorityGuan, XY=rp00454-
dc.identifier.authorityLaw, SYK=rp00437-
dc.identifier.authorityTsao, GSW=rp00399-
dc.identifier.authorityCheung, ALM=rp00332-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.18632/oncotarget.2596-
dc.identifier.pmid25344912-
dc.identifier.pmcidPMC4294385-
dc.identifier.scopuseid_2-s2.0-84917690897-
dc.identifier.hkuros242174-
dc.identifier.volume5-
dc.identifier.issue22-
dc.identifier.spage11576-
dc.identifier.epage11587-
dc.identifier.isiWOS:000348037400055-
dc.publisher.placeUnited States-

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