Talazoparib nanoparticles for overcoming multidrug resistance in triple-negative breast cancer


Eskiler G. G. , ÇEÇENER G., EGELİ Ü., TUNCA B.

JOURNAL OF CELLULAR PHYSIOLOGY, vol.235, no.9, pp.6230-6245, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 235 Issue: 9
  • Publication Date: 2020
  • Doi Number: 10.1002/jcp.29552
  • Journal Name: JOURNAL OF CELLULAR PHYSIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Agricultural & Environmental Science Database, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.6230-6245
  • Keywords: multidrug resistance (MDR), nanoparticles, solid lipid nanoparticles (SLNs), talazoparib, triple negative breast cancer (TNBC), SOLID LIPID NANOPARTICLES, PARP INHIBITOR TALAZOPARIB, MULTIPLE-DRUG RESISTANCE, P-GLYCOPROTEIN, DNA-REPAIR, BMN 673, OLAPARIB, CHEMORESISTANCE, COMBINATION, INVOLVEMENT
  • Bursa Uludag University Affiliated: Yes

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.