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Kombinacija elektrokemoterapije in zaviralcev poli (ADP-riboza) polimeraze (PARP) pri zdravljenju raka dojke
ID Janžič, Larisa (Author), ID Serša, Gregor (Mentor) More about this mentor... This link opens in a new window, ID Bošnjak, Maša (Co-mentor)

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Abstract
Elektrokemoterapija je kombinirana fizikalno-kemijska metoda, pri kateri z izpostavitvijo celic ali tkiva električnim pulzom povzročimo privzem citostatikov v celico. Je lokalna metoda zdravljenja z malo neželenimi učinki in nizko toksičnostjo. Kot najprimernejši zdravili sta se do sedaj izkazala bleomicin in cisplatin. Bleomicin je protitumorsko zdravilo, ki prek tvorbe dvojnih prelomov ustavlja celične delitve in povzroča smrt celic, cisplatin pa je alkilirajoči agens, ki v celicah primarno tvori adukte DNA, s tem pa prepreči podvojevanje DNA in nadaljnje delitve celic. V magistrski nalogi nas je zanimalo, ali se citotoksični učinek elektrokemoterapije poveča, če elektrokemoterapijo kombiniramo z olaparibom. Olaparib namreč zavirala popravljalni mehanizem PARP, ki ob nastanku enojnih in dvojnih prelomov rekrutira popravljalne mehanizme in omogoči popravljanje poškodb DNA. Citotoksično delovanje kombinacije smo preverili na humani celični liniji MCF-7 raka dojke, na 2D in 3D celičnih kulturah. Obetavne rezultate je prinesla kombinacija olapariba z elektrokemoterapijo z bleomicinom. Z barvanjem po Giemsi smo določili nastale morfološke spremembe. Z detekcijo žarišč ?-H2AX pa smo potrdili nastanek dvojnih prelomov po elektrokemoterapiji celic z bleomicinom in kombinaciji elektrokemoterapije z bleomicinom in olaparibom.

Language:Slovenian
Keywords:elektrokemoterapija, citostatiki, olaparib, citotoksičnost
Work type:Master's thesis/paper
Organization:BF - Biotechnical Faculty
Year:2019
PID:20.500.12556/RUL-109181 This link opens in a new window
COBISS.SI-ID:3445371 This link opens in a new window
Publication date in RUL:25.08.2019
Views:1170
Downloads:239
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Secondary language

Language:English
Title:Combination of electrochemotherapy and PARP inhibitors in breast cancer treatment
Abstract:
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.

Keywords:electrochemotherapy, cytostatics, olaparib, cytotoxicity

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