1. Talazoparib nanoparticles for overcoming multidrug resistance in triple-negative breast cancer
- Author
-
Berrin Tunca, Unal Egeli, Gulsah Cecener, Gamze Guney Eskiler, Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı., Çeçener, Gülşah, Egeli, Ünal, and Tunca, Berrin
- Subjects
Cell viability ,Cellular distribution ,Abcg2 ,Tumor protein ,0302 clinical medicine ,Olaparib ,Nanoparticle ,Pathology ,Triple-negative breast cancer ,Gene expression regulation ,Cancer resistance ,DNA-repair ,Messenger RNA ,MicroRNA 451a ,Drug transport ,Multidrug resistance-associated protein 1 ,Lipids ,ATP binding cassette transporter, subfamily G, member 2 ,Gene expression profiling ,Neoplasm proteins ,030220 oncology & carcinogenesis ,Reverse transcription polymerase chain reaction ,Efflux ,Solid lipid nanoparticle ,Chemoresistance ,Human ,MRNA expression level ,BMN 673 ,Multidrug resistance (MDR) ,P-glycoprotein ,Article ,Drug resistance, multiple ,Multidrug resistance associated protein ,03 medical and health sciences ,Breast cancer ,Drug formulation ,Genetics ,Humans ,Tumor cell line ,medicine.disease ,body regions ,Drug effect ,Solid lipid nanoparticles (SLNs) ,030104 developmental biology ,Cell line, tumor ,chemistry ,Human cell ,Gene expression regulation, neoplastic ,Drug resistance ,Nanoparticles ,Phthalazines ,Triple negative breast neoplasms ,Transmission electron microscopy ,0301 basic medicine ,Unclassified drug ,Physiology ,Talazoparib ,Clinical Biochemistry ,Immunofluorescence ,Ovarian Neoplasms ,Homologous Recombination ,Antiproliferative activity ,ABCB1 protein, human ,Multidrug resistance ,Western blotting ,chemistry.chemical_compound ,Phthalazine derivative ,Triple negative breast cancer ,ABCG2 protein, human ,Protein expression level ,Cellular localization ,Priority journal ,Multidrug resistance-associated proteins ,biology ,medicine.diagnostic_test ,Multiple-drug resistance ,MicroRNA ,Particle size ,Lipid ,Breast cancer resistance protein ,Chemistry ,Combination ,Female ,Drug sensitivity ,Cell biology ,Solid lipid nanoparticles ,MicroRNA 326 ,ATP binding cassette transporter, subfamily B ,MicroRNA 328 ,Triple negative breast cancer (TNBC) ,Western blot ,Drug resistance, neoplasm ,MicroRNA 298 ,medicine ,In vitro study ,Zeta potential ,Parp inhibitor talazoparib ,Calcein ,Multiple drug resistance ,Drug efficacy ,Doxorubicin ,biology.protein ,Cancer research ,Involvement ,Controlled study ,Multidrug resistance associated protein 1 - Abstract
Herein, we investigated efflux pumps-mediated talazoparib-resistance in the treatment of triple-negative breast cancer (TNBC). Furthermore, we produced a novel talazoparib-solid lipid nanoparticles (SLNs) and then explored in vitro therapeutic efficacy of talazoparib-SLNs to overcome talazoparib-resistance in TNBC cells. Talazoparib-SLNs formulation was produced and then characterized. Calcein and Rho-123 were used to analyze the functional activity of drug efflux pumps in these cells. Additionally, RT-PCR, western blot and immunofluorescence analysis were used to detect the messenger RNA, and protein expression level, and cellular localization of the multidrug resistance (MDR1), breast cancer resistance protein (BCRP), and MRP1. We found that talazoparib efflux was mediated by BCRP and MRP1 pumps in TNBC cells. Talazoparib-SLNs could significantly enhance therapeutic efficacy of talazoparib. Furthermore, talazoparib-SLNs were more effective in the suppression of MDR1, BCRP, and MRP1 gene and protein expression levels than talazoparib. Consequently, this study suggests that talazoparib-SLNs formulation represents a promising therapeutic carrier to reverse MDR-mediated resistance in TNBC.
- Published
- 2020