20.500.12556/DiRROS-15564 PARP inhibitor olaparib has a potential to increase the effectiveness of electrochemotherapy in BRCA1 mutated breast cancer in mice Electrochemotherapy (ECT), a local therapy, has different effectiveness among tumor types. In breast can-cer, its effectiveness is low; therefore, combined therapies are needed. The aim of our study was to com-bine ECT with PARP inhibitor olaparib, which could inhibit the repair of bleomycin or cisplatin inducedDNA damage and potentiate the effectiveness of ECT. The effects of combined therapy were studied inBRCA1mutated (HCC1937) and non-mutated (HCC1143) triple negative breast cancer cell lines.Therapeutic effectiveness was studied in 2D and 3D cell cultures andin vivoon subcutaneousHCC1937 tumor model in mice. The underlying mechanism of combined therapy was determined withthe evaluation ofcH2AX foci. Combined therapy of ECT with bleomycin and olaparib potentiated theeffectiveness of ECT inBRCA1mutated HCC1937, but not in non-mutated HCC1143 cells. The combinedtherapy had a synergistic effect, which was due to the increased number of DNA double strand breaks.Addition of olaparib to ECT with bleomycinin vivoin HCC1937 tumor model had only minimal effect,indicating repetitive olaparib treatment would be needed. This study demonstrates that DNA repar inhibiting drugs, like olaparib, have the potential to increase the effectiveness of ECT with bleomycin. electrochemotherapy breast cancer olaparib bleomycin elektrokemoterapija rak dojke olaparib bleomycin true false true Elsevier Angleški jezik Slovenski jezik by Authors Neznano 2022-09-21 03:35:08 2022-09-21 09:46:51 2022-09-22 03:43:32 0000-00-00 00:00:00 2021 0 0 str. 107832-1-10783-12 Vol. 140 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2021-05-01 602.6/.7 1567-5394 10.1016/j.bioelechem.2021.107832 66822915 RAZ_Bosnjak_Masa_2021.pdf RAZ_Bosnjak_Masa_2021.pdf 1 1B2A7A6917FD419DB6A245FCA0640FF5 a89bdf43e765a64f79eb74782dacdff2a12e0e9469fab3a662c7ae2dba2a088f 497398ce-3972-11ed-bea5-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=20592 Onkološki inštitut Ljubljana 0 0 0