Olaparib potentiates doxorubicin effect in BRCA-proficient MDA-MB-231 breast cancer cell line

SOTTILE ML; TRONCOSO ME; REDONDO AL; DE CAMPOS NEBEL M; VARGAS ROIG LM

Palma de Mallorca

Workshop; 2nd International Workshop on Translational Cancer Research; 2021

Background and aims. Breast cancer (BC) is the leading cause of cancer death in women in Argentina. Anthracycline-based regimens are efficaciously used in BC treatment. However, chemotherapy resistance development and adverse effects are still a challenge for the oncology. Poly [ADP-ribose] polymerase (PARP) is a key DNA repair protein mainly involved in base excision repair. Last years, PARP inhibitors (PARPi) have been approved for the treatment of BRCA-mutated BC. As PARP is involved in doxorubicin-induced cellular response, the aim of this work was to determine the effect of the PARPi olaparib on the sensitivity of BC cells to the anthracycline doxorubicin. Methods. MDA-MB-231 cells were treated with increasing concentrations of doxorubicin (2.5-40 nM), olaparib (1 µM) or doxorubicin and olaparib during 24 h. Clonogenic assay and viability assay were performed. Pharmacological interaction was analysed based on Chou-Talalay method. Immunofluorescence of γH2AX was conducted to evaluate DNA damage immediately after treatment and 24 h after recovery at 37 °C. Results. Simultaneous administration of the drugs resulted in a combination index