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Synthesis and biological activity of siRNA and Etoposide with magnetic nanoparticles on drug resistance model MCF-7 Cells: Molecular docking study with MRP1 enzyme    
Yazarlar (2)
Prof. Dr. Serap YALÇIN AZARKAN Prof. Dr. Serap YALÇIN AZARKAN
Kırşehir Ahi Evran Üniversitesi, Türkiye
Ufuk Gündüz
Middle East Technical University, Türkiye
Devamını Göster
Özet
Objective(s): In this work, MRP-1 (Multidrug resistance-associated protein 1) gene expression levels and anticancer activity of siRNA and Etoposide loaded Poly-hydroxybutyrate (PHB) coated magnetic nanoparticles (MNPs) was studied on MCF-7/Sensitive and MCF-7/1000 Etoposide resistance cells. For this purpose, PHB covered iron oxide-based magnetic nanoparticles (PHB-MNPs) were prepared by coprecipitation. We used magnetic nanoparticles because they include highly targeted to tumors in vivo cancer therapy.
Materials and Methods: Etoposide, anti-cancer drug, was loaded onto the PHB-MNPs. The in vitro cytotoxicity analysis of siRNA and Etoposide-loaded PHB-MNPs was applied on cancer cells. The expression levels of MRP1 related to drug resistance were shown using qRT-PCR. In the present study, we also investigated whether nanoparticle system could be a potential anticancer drug target with molecular docking analyses.
Results: The IC50 values of Etoposide on MCF-7/sensitive and MCF-7/1000 Eto resistance cells were identified as 50,6 mu M and 135,7 mu M, respectively. IC50 values of siRNA and Etoposide loaded PHB coated magnetic nanoparticles were determined as 10,18 mu M and 39,21 mu M on MCF-7 and MCF-7/1000 Eto cells, respectively. According to the gene expression results, MRP1 expression was 4 fold upregulated in MCF-7/1000 Eto cells. However, it was about 3 fold downregulated due to the application of siRNA-Etoposide loaded magnetic nanoparticles.
Conclusion: According to the docking results, nanoparticle system may be a drug active substance with obtained results. The results of this study demonstrated that siRNA and Etoposide loaded PHB covered iron oxide based magnetic nanoparticles can be a potential targeted therapeutic agent to overcome drug resistance.
Anahtar Kelimeler
Anticancer effect | Breast Cancer | Etoposide | Molecular docking | PHB coated magnetic nanoparticles | siRNA
Makale Türü Özgün Makale
Makale Alt Türü ESCI dergilerinde yayınlanan tam makale
Dergi Adı NANOMEDICINE JOURNAL
Dergi ISSN 2322-3049 Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler E-SCI
Makale Dili Türkçe
Basım Tarihi 04-2021
Cilt No 8
Sayı 2
Sayfalar 98 / 105
DOI Numarası 10.22038/nmj.2021.08.002
Makale Linki https://nmj.mums.ac.ir/article_17514.html