Eskiler, Gamze Güney2023-02-062023-02-062020-02-03Eskiler, G. G. vd. (2020). "Talazoparib nanoparticles for overcoming multidrug resistance in triple-negative breast cancer". Journal of Cellular Physiology, 235(9), 6230-6245.0021-95411097-4652https://doi.org/10.1002/jcp.29552https://onlinelibrary.wiley.com/doi/10.1002/jcp.29552http://hdl.handle.net/11452/30840Herein, 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.eninfo:eu-repo/semantics/closedAccessCell biologyPhysiologyMultidrug resistance (MDR)NanoparticlesSolid lipid nanoparticles (SLNs)TalazoparibTriple negative breast cancer (TNBC)Solid lipid nanoparticlesParp inhibitor talazoparibMultiple-drug resistanceP-glycoproteinDNA-repairBMN 673OlaparibChemoresistanceCombinationInvolvementATP binding cassette transporter, subfamily BATP binding cassette transporter, subfamily G, member 2Cell line, tumorDoxorubicinDrug resistance, multipleDrug resistance, neoplasmFemaleGene expression regulation, neoplasticHumansLipidsMultidrug resistance-associated proteinsNanoparticlesNeoplasm proteinsPhthalazinesTriple negative breast neoplasmsArticle0005106302000012-s2.0-8507895821762306245235932017076Cell biologyPhysiologyOlaparib; Ovarian Neoplasms; Homologous RecombinationBreast cancer resistance proteinMessenger RNAMicroRNAMicroRNA 298MicroRNA 326MicroRNA 328MicroRNA 451aMultidrug resistance associated protein 1Solid lipid nanoparticleTalazoparibUnclassified drugABCB1 protein, humanABCG2 protein, humanDoxorubicinLipidMultidrug resistance associated proteinMultidrug resistance-associated protein 1NanoparticlePhthalazine derivativeTalazoparibTumor proteinAntiproliferative activityArticleCancer resistanceCell viabilityCellular distributionControlled studyDrug efficacyDrug formulationDrug sensitivityDrug transportGene expression profilingHumanHuman cellImmunofluorescenceIn vitro studyMRNA expression levelMultidrug resistanceParticle sizePriority journalProtein expression levelReverse transcription polymerase chain reactionTransmission electron microscopyTriple negative breast cancerWestern blottingZeta potentialChemistryDrug effectDrug resistanceFemaleGene expression regulationGeneticsMultidrug resistancePathologyTriple negative breast cancerTumor cell line