Electrochemotherapy is a physical delivery method, where cells or tissues are exposed to electric pulses, which increase the uptake of cytotoxic drugs into cells. It is a local ablative treatment method with almost negligible side effects and high antitumor effectiveness. Among many tested substances, only bleomycin and cisplatin have been mainly used. Bleomycin is an anti-cancer drug, which inhibits cell divisions by forming double strand breaks, whereas cisplatin is an alkylating agent that forms DNA aducts and inhibits DNA replication and cell divisions. The aim of the study was to investigate if the combination of electrochemotherapy with bleomycin or cisplatin and olaparib, which is a PARP inhibitor, has a greater cytotoxic effect than only electrochemotherapy. PARP is a repair mechanism that recruits other repair mechanisms when single and double strand breaks occur. We evaluated the effects of the combined treatment on human breast cancer cell line MCF-7. We observed promising effects of combining electrochemotherapy with bleomycin and olaparib, proving that the combination highly decreases cancer cell growth. We used 2D and 3D cell cultures. Giemsa staining showed morphological changes, whereas the detection of ?-H2AX confirmed formation of double strand breaks after electrochemotherapy with bleomycin alone or in combination with olaparib.
|
