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Regulation of MRP1 gene expression by etoposide-loaded PHB coated magnetic nanoparticles in Etoposide resistance MCF-7 cells
Proje Ekibi
Prof. Dr. Serap YALÇIN AZARKAN
Kırşehir Ahi Evran Üniversitesi, Türkiye
Projedeki Rolü: Yürütücü
Proje Türü (Ulusal) Yükseköğretim Kurumları Tarafından Destekli Bilimsel Araştırma Projesi
Proje No FEF.E2.17.018
Proje Konusu Background: Magnetic iron oxide nanoparticles (MNPs), being biodegradable and suitable for surface modifications, are the most prominent class of MNPs for biomedical applications such as magnetic resonance imaging, magnetic hyperthermia for cancer treatment and tissue-specific delivery of therapeutic agents. The aim of this study is to investigate MRP1 gene expression levels and anticancer activity of Etoposide loaded PHB coated magnetic nanoparticles on MCF-7/S and MCF-7/1000Eto cells. Materials and Methods: For this purpose, polyhydroxybutyrate (PHB)-coated magnetic nanoparticles (PHB-MNPs) were prepared by coprecipitation of iron salts (Fe2+ and Fe3+) by ammonium hydroxide. The novel synthesized PHB-MNPs, which have targeting potential under magnetic field, were characterized by FTIR, VSM, and TEM analyses. Etoposide was loaded onto the PHB-MNPs. The in vitro cytotoxicity analysis of Etoposide-loaded PHB-MNPs was performed on MCF-7/S and MCF-7/1000Eto cells. Total RNA content was isolated by TRI Reagent according to the manufacturer's instructions. cDNA was synthesized from 1 ug of total RNA and random hexamer primers. The expression levels of MRP1 related to drug resistance were shown using qRT-PCR. Results: IC50 value of MCF-7 and MCF-7/1000Eto cells were identified as 50,6 μM and 135,7 μM, respectively. MCF-7/1000Eto cells are 2.7 fold resistant to etoposide relative to parental MCF-7/S cell line. IC50 values of Etoposide loaded PHB coated magnetic nanoparticles were identified as 11,53 μM and 42,78 μM on MCF-7 and MCF-7/1000 Eto cells, respectively. According to the gene expression results, MRP1 expression was 4 fold upregulated in MCF-7/1000Eto cells. However, it was 2 fold downregulated due to the application of Etoposide loaded magnetic nanoparticles. Conclusion: The results of this study demonstrated that Etoposide loaded PHB coated magnetic nanoparticles can be a potential targeted therapeutic agent to overcome drug resistance.
Proje Durumu Tamamlandı
Başlangıç Tarihi 09-03-2017
Bitiş Tarihi 06-06-2017
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