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Anti-tumor effects of NVP-BKM120 alone or in combination with MEK162 in biliary tract cancer

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dc.contributor.authorJin, Ling-
dc.contributor.authorJin, Mei-hua-
dc.contributor.authorNam, Ah-Rong-
dc.contributor.authorPark, Ji-Eun-
dc.contributor.authorBang, Ju-Hee-
dc.contributor.authorOh, Do Yeun-
dc.contributor.authorBang, Yung Jue-
dc.date.accessioned2021-01-31T11:58:08Z-
dc.date.available2021-01-31T11:58:08Z-
dc.date.issued2017-12-
dc.identifier.citationCancer Letters, Vol.411, pp.162-170-
dc.identifier.issn0304-3835-
dc.identifier.other37104-
dc.identifier.urihttps://hdl.handle.net/10371/173169-
dc.description.abstractThere are currently no clinically validated therapeutic targets for biliary tract cancer (BTC). Despite promising results in other cancers, compounds targeting the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, alone or in combination with Ras/Raf/MEK pathway inhibitors, have not been evaluated in BTC. Here, we examined the effects of a pan-PI3K inhibitor (BKM120) with or without a MEK inhibitor (MEK162), on eight human BTC cell lines carrying mutations in K-Ras and/or the PI3K catalytic subunit, P13KCA. BKM120 inhibited the colony-forming ability and migration of BTC cells carrying wild-type (WT) PI3KCA and either mutant (MT) or WT K-Ras, but not of cells carrying mutations in both genes. In K-Ras-WT cells, BKM120 decreased the phosphorylation of Akt, its downstream effector kinase p70S6K, and the translational repressor 4E-BP1. Interestingly, BKM120 did not induce cell cycle arrest or suppress PI3K signaling via restoration of p-4E-BP1 in cells with PIK3CA and K-Ras double mutations. Notably, the resistance of dual K-Ras/PI3KCA-mutant cells to BKM120 was overcome by treatment with a combination of BKM120 and MEK162. Our findings thus support the clinical development of BKM120 monotherapy or BKM120/MEK162 combination therapy for the treatment of BTC. (c) 2017 Elsevier B.V. All rights reserved.-
dc.subjectPI3K inhibitor-
dc.subjectMEK inhibitor-
dc.subjectK-Ras-
dc.subjectBiliary tract cancer-
dc.titleAnti-tumor effects of NVP-BKM120 alone or in combination with MEK162 in biliary tract cancer-
dc.typeArticle-
dc.contributor.AlternativeAuthor방영주-
dc.identifier.doi10.1016/j.canlet.2017.10.002-
dc.citation.journaltitleCancer Letters-
dc.identifier.scopusid2-s2.0-85031774673-
dc.citation.endpage170-
dc.citation.startpage162-
dc.citation.volume411-
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0304383517306250?via%3Dihub-
dc.identifier.rimsid37104-
dc.identifier.sci000416299700019-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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