The effects of low-dose sorafenib on epithelial-mesenchymal transition and multidrug resistance markers in HepG2 cell line

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dc.authorid0000-0002-4605-1167en_US
dc.authorid0000-0002-7526-8496en_US
dc.authorid0000-0002-5501-3736en_US
dc.authorid0000-0002-3060-1507en_US
dc.authorid0000-0002-4474-7371en_US
dc.contributor.authorDönmez Çakıl, Yaprak
dc.contributor.authorAkbulut, Zeynep
dc.contributor.authorDemirel, Gamze
dc.contributor.authorGüneş Özünal, Zeynep
dc.contributor.authorAktaş, Gülhan Ranan
dc.date.accessioned2024-07-12T21:11:22Z
dc.date.available2024-07-12T21:11:22Z
dc.date.issued2023en_US
dc.departmentFakülteler, Tıp Fakültesien_US
dc.description.abstractObjectives: Sorafenib is an orally administered tyrosine kinase inhibitor in hepatocellular cancer. Low sorafenib concentrations are attained during pharmacotherapy due to pharmacokinetic profile and patient inadherence. Resistance to treatment is a limitation to improving survival. Underlying mechanisms include epithelial-mesenchymal transition. The aim of the study was to evaluate epithelial-mesenchymal transition and multidrug resistance-related parameters in HepG2 cells following low-dose and short-term sorafenib treatment. Methods: Epithelial-mesenchymal transition and multidrug resistance-related markers were examined by quantitative PCR, flow cytometry, and confocal laser scanning microscopy. Results: An increase in epithelial marker E-cadherin and downregulation of mesenchymal markers Vimentin and Snail1 were detected by gene expression analysis. While P-glycoprotein expression increased, multidrug resistance protein 1, and breast cancer resistance protein mRNA levels did not alter after sorafenib treatment. The accumulation of the ABC transporter substrate rhodamine 123 in the cells increased following the treatment, corresponding to a less efficient efflux of rhodamine 123 and a possible effect on other transporters and mechanisms. Conclusions: The results indicate a protective effect of sorafenib against epithelial-mesenchymal transition and upregulation in P-glycoprotein expression, which is, however, not sufficient to cause less intracellular rhodamine 123 accumulation. The effects of low-dose and short-term sorafenib on epithelial-mesenchymal transition and multidrug resistance-related markers might contribute to enlightening new treatment strategies in hepatocellular cancer.en_US
dc.identifier.citationDönmez Çakıl, Y., Akbulut, Z., Demirel, G. vd. (2023). The effects of low-dose sorafenib on epithelial-mesenchymal transition and multidrug resistance markers in HepG2 cell line. The European Research Journal, Prusa Medical Publishing. 9(2), s. 367-374.en_US
dc.identifier.doi10.18621/eurj.1206680
dc.identifier.endpage374en_US
dc.identifier.issn2149-3189
dc.identifier.issue2en_US
dc.identifier.startpage367en_US
dc.identifier.trdizinid1158541en_US
dc.identifier.urihttps://dergipark.org.tr/en/pub/eurj/issue/75618/1206680
dc.identifier.urihttps://doi.prg/10.18621/eurj.1206680
dc.identifier.urihttps://hdl.handle.net/20.500.12415/4364
dc.identifier.volume9en_US
dc.indekslendigikaynakTR-Dizin
dc.institutionauthorDönmez Çakıl, Yaprak
dc.institutionauthorAkbulut, Zeynep
dc.institutionauthorDemirel, Gamze
dc.institutionauthorGüneş Özünal, Zeynep
dc.institutionauthorAktaş, Gülhan Ranan
dc.language.isoenen_US
dc.publisherPrusa Medical Publishingen_US
dc.relation.ispartofThe European Research Journalen_US
dc.relation.publicationcategoryUluslararası Hakemli Dergide Makale - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmzKY03516
dc.subjectSorafeniben_US
dc.subjecthepatocellular canceren_US
dc.subjectHepG2en_US
dc.subjectmultidrug resistanceen_US
dc.subjectepithelial-mesenchymal transitionen_US
dc.titleThe effects of low-dose sorafenib on epithelial-mesenchymal transition and multidrug resistance markers in HepG2 cell lineen_US
dc.typeArticle
dspace.entity.typePublication

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