Občutljivost sferoidov hormonsko pozitivnega raka dojke na tamoksifen in kanabidiol

Stanovšek, Katja (author), Čemažar, Maja (mentor), Kranjc Brezar, Simona (comentor)

Zaradi velike pojavnosti raka dojke v populaciji in tudi velike umrljivosti pri ženskah smo v magistrski nalogi raziskali občutljivost sferoidov hormonsko pozitivnega raka dojke MCF-7 na tamoksifen, ki je pogost kemoterapevtik pri hormonskem zdravljenju, in kanabidiol, ki je pogost del paliativnega zdravljenja. Sferoide smo izpostavili izbranim koncentracijam tamoksifena (7,5 μM, 15 μM, 22,5 μM) ter običajnega ali vodotopnega kanabidiola (30 μM, 60 μM, 90 μM) in njihovim kombinacijam. Sferoide smo z napravo Cytation1 spremljali do sedmega dne po izpostavitvi in določili njihovo dnevno prirast. Izvedli smo test metabolne aktivnosti celic v sferoidih z reagentom PrestoBlue, določili deleže mitoze, apoptoze in nekrotičnega področja v sferoidih s pregledom histoloških preparatov. Izvedli smo tudi test migracije in test invazije. Izpostavitev testnim učinkovinam je povzročila dozno odvisen učinek na rast sferoidov. Izpostavitev kombinaciji najvišjih testiranih koncentracij tamoksifena in vodotopnega kanabidiola je najbolj upočasnila rast sferoidov. Ta izpostavitev je tudi najbolj zmanjšala metabolno aktivnost celic v sferoidih, od vseh izpostavitev je povzročila največji delež apoptotičnih celic v sferoidih in največ nekroze. Za zmanjšanje sposobnosti migracije celic sta se kot enako dobra in od vseh testiranih izpostavitev kot najbolj učinkovita izkazala oba kanabidiola v kombinaciji s tamoksifenom. Od izpostavitev posameznim testnim učinkovinam v izbranih koncentracijah so bili sferoidi hormonsko pozitivnega raka dojke MCF-7 najbolj občutljivi na vodotopni kanabidiol.

• Language: Slovenian
• Keywords: rak dojke, tamoksifen, kanabidiol, MCF-7, sferoidi
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: BF - Biotechnical Faculty
• Publisher: [K. Stanovšek]
• Year: 2025
• PID: 20.500.12556/RUL-168761
• UDC: 616-006(043.2)
• COBISS.SI-ID: 234105603
• Publication date in RUL: 24.04.2025

Secondary language

• Language: English
• Title: Sensitivity of hormone-positive breast cancer spheroids to tamoxifen and cannabidiol

Abstract

Due to the high incidence of breast cancer in the population and also the high mortality rate in women, we investigated the sensitivity of the spheroids of hormone-positive breast cancer MCF-7 to tamoxifen, which is a common chemotherapeutic agent in hormone therapy, and cannabidiol, which is a common part of palliative treatment. Spheroids were treated with selected concentrations of tamoxifen (7.5 μM, 15 μM, 22.5 μM), ordinary or water-soluble cannabidiol (30 μM, 60 μM, 90 μM) and their combinations. The spheroids were monitored with the Cytation1 device until the seventh day after exposure and their daily growth was determined. We performed a test of the metabolic activity of cells in spheroids with the PrestoBlue reagent. We determined the proportions of mitosis, apoptosis and necrotic area in spheroids by examining histological slides. We also conducted a migration test and an invasion test. The exposure to test substances produced a dose-dependent effect on spheroid growth. Exposure to the combination of the highest tested concentrations of tamoxifen and water-soluble cannabidiol inhibited spheroid growth the most. This exposure also reduced the metabolic activity of cells in the spheroids the most, resulted in the highest proportion of apoptotic cells in the spheroids and the highest proportion of necrosis of all exposures. For reducing the migratory abilities of cells, both cannabidiols in combination with tamoxifen proved to be equally good, and of all the tested exposures, the most effective. Of the exposures to individual active substances in selected concentrations, the spheroids of hormone-positive breast cancer MCF-7 were the most sensitive to water-soluble cannabidiol.

• Keywords: breast cancer, tamoxifen, cannabidiol, MCF-7, spheroids