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.authorOzdemir Kutbay N.
dc.contributor.authorBiray Avci C.
dc.contributor.authorSarer Yurekli B.
dc.contributor.authorCaliskan Kurt C.
dc.contributor.authorShademan B.
dc.contributor.authorGunduz C.
dc.contributor.authorErdogan M.
dc.date.accessioned2024-07-22T08:07:02Z
dc.date.available2024-07-22T08:07:02Z
dc.date.issued2020
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 RT2 Profiler PCR Array. In C643 and SW1736 cell lines, IC50 doses of MET and PIO were found out as 17.69 mM, 11.64 mM, 27.12 µM, and 23.17 µM. 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, and RICTOR genes, in the MET and PIO combination-treated cells. In addition, expression levels of tumor suppressor genes, DDIT4, DDIT4L, EIF4EBP1, EIF4EBP2, FKBP1A, FKBP8, GSK3B, MYO1C, PTEN, ULK1, and ULK2, 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, in AKT3, DEPTOR, EIF4E, ILK, MTOR, PIK3C, and PRKCA expressions indicate that progression can be prevented in thyroid cancer cells and these genes could be selected as therapeutic targets. © 2020 Wiley Periodicals LLC
dc.identifier.DOI-ID10.1002/jbt.22547
dc.identifier.issn10956670
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/13790
dc.language.isoEnglish
dc.publisherJohn Wiley and Sons Inc
dc.subjectAMP-Activated Protein Kinases
dc.subjectApoptosis
dc.subjectCell Line, Tumor
dc.subjectDrug Therapy, Combination
dc.subjectGene Expression
dc.subjectHumans
dc.subjectMetformin
dc.subjectPioglitazone
dc.subjectSignal Transduction
dc.subjectThyroid Carcinoma, Anaplastic
dc.subjectThyroid Neoplasms
dc.subjectTOR Serine-Threonine Kinases
dc.subjectakt3 protein
dc.subjectconserved helix loop helix ubiquitous kinase
dc.subjectddit4 protein
dc.subjectddit4l protein
dc.subjecteif4ebp1 protein
dc.subjecteif4ebp2 protein
dc.subjectfk506 binding protein 8
dc.subjectfkbp1a protein
dc.subjectglycogen synthase kinase 3beta
dc.subjecthypoxia inducible factor 1alpha
dc.subjectI kappa B kinase beta
dc.subjectinitiation factor 4E
dc.subjectintegrin linked kinase
dc.subjectmammalian target of rapamycin
dc.subjectmetformin
dc.subjectmyo1c protein
dc.subjectphosphatidylinositol 3,4,5 trisphosphate 3 phosphatase
dc.subjectphospholipase D1
dc.subjectphosphotransferase
dc.subjectpik3ca protein
dc.subjectpik3cg protein
dc.subjectpioglitazone
dc.subjectprkca protein
dc.subjectprotein Cdc42
dc.subjectrapamycin-insensitive companion of mTOR
dc.subjectserine threonine protein kinase ULK1
dc.subjectserine threonine protein kinase ULK2
dc.subjecttumor suppressor protein
dc.subjectunclassified drug
dc.subjecthydroxymethylglutaryl coenzyme A reductase kinase
dc.subjectmetformin
dc.subjectMTOR protein, human
dc.subjectpioglitazone
dc.subjecttarget of rapamycin kinase
dc.subjectAMPK signaling
dc.subjectanaplastic thyroid carcinoma
dc.subjectapoptosis
dc.subjectArticle
dc.subjectC-643 cell line
dc.subjectcell viability
dc.subjectcombination index
dc.subjectcontrolled study
dc.subjectdown regulation
dc.subjectdrug mechanism
dc.subjectevaluation study
dc.subjectgene expression level
dc.subjecthuman
dc.subjecthuman cell
dc.subjectIC50
dc.subjectmTOR signaling
dc.subjectSW1736 cell line
dc.subjectWST-1 assay
dc.subjectapoptosis
dc.subjectcombination drug therapy
dc.subjectdrug effect
dc.subjectgene expression
dc.subjectmetabolism
dc.subjectpathology
dc.subjectsignal transduction
dc.subjectthyroid carcinoma
dc.subjectthyroid tumor
dc.subjecttumor cell line
dc.titleEffects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells
dc.typeArticle

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