The effects of low-dose sorafenib on epithelial-mesenchymal transition and multidrug resistance markers in HepG2 cell line
Küçük Resim Yok
Tarih
2023
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Prusa Medical Publishing
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Objectives: 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.
Açıklama
Anahtar Kelimeler
Sorafenib, hepatocellular cancer, HepG2, multidrug resistance, epithelial-mesenchymal transition
Kaynak
The European Research Journal
WoS Q Değeri
Scopus Q Değeri
Cilt
9
Sayı
2
Künye
Dönmez 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.
