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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
 Serap YALÇIN AZARKAN Serap YALÇIN AZARKAN
Kırşehir Ahi Evran Üniversitesi, Türkiye
Ufuk Gündüz
Türkiye
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 yayımlanan tam makale
Dergi Adı NANOMEDICINE JOURNAL
Dergi ISSN 2322-3049
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