Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells

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dc.contributor.authorKutbay, Nilufer Ozdemir
dc.contributor.authorAvci, Cigir Biray
dc.contributor.authorYurekli, Banu Sarer
dc.contributor.authorKurt, Cansu Caliskan
dc.contributor.authorShademan, Behrouz
dc.contributor.authorGunduz, Cumhur
dc.contributor.authorErdogan, Mehmet
dc.date.accessioned2020-12-01T11:59:18Z
dc.date.available2020-12-01T11:59:18Z
dc.date.issued2020
dc.departmentEge Üniversitesien_US
dc.description.abstractAnaplastic cancer constitutes 1% of thyroid cancers, and it is one of the most aggressive cancers. Treatment options are external radiation therapy and/or chemotherapy. the success rate with these treatment modalities is not satisfactory. We aimed to evaluate the effects of metformin (MET) and pioglitazone (PIO) combination on apoptosis and AMP-activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway in human anaplastic thyroid cancer cells. in this study, we evaluated the effects of MET and PIO individually and the combination of the two drugs on the cellular lines SW1736 and C643 ATC. Genes contained in the mTOR signaling pathway were examined using human mTOR Signalization RT(2)Profiler PCR Array. in C643 and SW1736 cell lines, IC(50)doses of MET and PIO were found out as 17.69 mM, 11.64 mM, 27.12 mu M, and 23.17 mu M. Also, the combination of MET and PIO was determined as an additive according to isobologram analyses. We have found the downregulation of the expression levels of oncogenic genes:AKT3, CHUK, CDC42, EIF4E, HIF1A, IKBKB, ILK, MTOR, PIK3CA, PIK3CG, PLD1, PRKCA, andRICTORgenes, in the MET and PIO combination-treated cells. in addition, expression levels of tumor suppressorgenes, DDIT4, DDIT4L, EIF4EBP1, EIF4EBP2, FKBP1A, FKBP8, GSK3B, MYO1C, PTEN, ULK1, andULK2, were found to have increased significantly. the MET + PIO combination was first applied to thyroid cancer cells, and significant reductions in the level of oncogenic genes were detected. the decreases, particularly, inAKT3, DEPTOR, EIF4E, ILK, MTOR, PIK3C, andPRKCAexpressions indicate that progression can be prevented in thyroid cancer cells and these genes could be selected as therapeutic targets.en_US
dc.description.sponsorshipEge Universitesi [2014-TIP-013]en_US
dc.description.sponsorshipEge Universitesi; This study relies on Ege University coordinatorship of scientific research projects (2014-TIP-013) Account Holder: Mehmet Erdoganen_US
dc.identifier.doi10.1002/jbt.22547en_US
dc.identifier.issn1095-6670
dc.identifier.issn1099-0461
dc.identifier.issue10en_US
dc.identifier.pmid32589349en_US
dc.identifier.scopus2-s2.0-85087147773en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1002/jbt.22547
dc.identifier.urihttps://hdl.handle.net/11454/62227
dc.identifier.volume34en_US
dc.identifier.wosWOS:000543153300001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofJournal of Biochemical and Molecular Toxicologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectapoptosisen_US
dc.subjectcell linesen_US
dc.subjectmetforminen_US
dc.subjectpioglitazoneen_US
dc.subjectsignaling pathwayen_US
dc.subjectthyroid canceren_US
dc.titleEffects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cellsen_US
dc.typeArticleen_US

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