BCRP and P-gp relay overexpression in triple negative basal-like breast cancer cell line: a prospective role in resistance to Olaparib

Abstract

The triple negative basal-like (TNBL) breast carcinoma is an aggressive and unfavorable prognosis disease. Inhibitors of poly(ADP-ribose) polymerase such as Olaparib could represent a promising targeted therapy but their sensitivity against Multidrug Resistance proteins (MDR), which causes resistance, is not well defined. Thus, our work focused on the analysis of P-gp and BCRP coexpression in the SUM1315 TNBL human cell line, in correlation with Olaparib intracellular concentration. Western blot analyses showed a clear coexpression of P-gp and BCRP in SUM1315 cells. A low cytotoxic Olaparib treatment clearly led to an increased expression of both BCRP and P-gp in these cells. Indeed, after 1.5 h of treatment, BCRP expression was increased with a 1.8 fold increase rate. Then, P-gp took over from 3 h to 15 h with an average increase rate of 1.8 fold, and finally returned to control value at 24 h. HPLC-UV analyses showed that, in the same treatment conditions, the intracellular Olaparib concentration increased from 1 h to 3 h and remained relatively stable until 24 h. Results suggest that the resistance mechanism induced by Olaparib in TNBL SUM1315 cell line may be overpassed if a cytotoxic and stable intracellular level of the drug can be maintained.