Title Djelovanje tripiridilporfirina na stanice melanoma Title (english) Effect of tripyridylporphyrin on melanoma cells Author Laura Penić-Ivanko Mentor Ivana Ratkaj (mentor) Committee member Rozi Andretić Waldowski (član povjerenstva) Committee member Nela Malatesti (predsjednik povjerenstva) Granter University of Rijeka Defense date and country 2020-09-23, Croatia Scientific / art field, BIOTECHNICAL SCIENCES Abstract Melanom je maligni tumor melanocita te je zbog svoje agresivnosti i metastatske prirode ujedno i najsmrtonosniji oblik raka kože. Liječenje melanoma uključuje kirurški zahvat, kemoterapiju, radioterapiju, biološku terapiju te lijekove koji specifično ciljaju mutacije povezane s melanomom. Nedostatak ovakvih oblika liječenja je nemogućnost nadilaženja rezistencije melanoma te su iz tog razloga današnja istraživanja usmjerena prema korištenju fotodinamičke terapije kao sigurne i učinkovite terapije. Fotodinamička terapija temelji se na reakciji svjetlosti određene valne duljine, lijeka osjetljivog na svjetlost (fotosenzibilizatora) i molekule kisika, pri čemu nastaju reaktivni kisikovi spojevi koji djeluju citotoksično. Brojnim istraživanjima dokazana je djelotvornost fotodinamičke terapije u liječenju melanoma, međutim još uvijek se provode istraživanja kako bi se pronašao najučinkovitiji fotosenzibilizator. Najčešće se proučavaju ciklički tetrapiroli, kao što su porfirini ispitani u ovom radu. U radu su korištena četiri amfifilna metilirana porfirina sa različitim duljinama lanca, 10C-M, 14C-M, 18C-M i AMIDO-MET. Cilj ovog istraživanja je odrediti djelovanje navedenih spojeva na stanice melanoma (MEWO) i fibroblasta (HFF) te utvrditi koji spoj pokazuje najbolji učinak. MTT testom dokazano je da spoj 18C-M u najvećoj mjeri smanjuje proliferaciju stanica, dok spoj AMIDO-MET ne utječe na proliferaciju. Fluorescentnim mikroskopom praćena je lokalizacija porfirina u stanicama te je utvrđeno da spojevi 10C-M, 14C-M i 18C-M ulaze u stanicu i nakupljaju se u citoplazmi, a prema intenzitetu crvenog obojenja utvrđeno je da se najviše nakuplja 18C-M. Zbog najveće duljine lanca, a samim time i najveće lipofilnosti, dokazano je da je spoj 18C-M najučinkovitiji fotosenzibilizator. Također, dokazano je da su spojevi podjednako učinkoviti u uvjetima sa i bez hipoksije te da nisu toksični u mraku.
Abstract (english) Melanoma is a malignant tumor of melanocytes and due to its aggressive as well as metastatic nature it is the deadliest form of skin cancer. Treatment of melanoma includes surgery, chemotherapy, radiotherapy, biological therapy, and drugs, which specifically target mutations associated with melanoma. The disadvantage of these therapies is inability to overcome resistance of melanoma and, because of that, studies are focused on using photodynamic therapy as a safe and effective therapy. Photodynamic therapy uses light of a certain wavelength, light-sensitive drug (photosensitizer) and oxygen molecule to form cytotoxic reactive oxygen species. Numerous studies have proven the effectiveness of photodynamic therapy in the treatment of melanoma; however, research is still being made to find the most effective photosensitizer. The most investigated photosensitizers are tricyclic tetrapyrroles, like porphyrins used in this study. Four methylated porphyrins with different chain lengths, 10C-M, 14C-M, 18C-M i AMIDO-MET, were used in this study. The aim of the study is to determine the effect of these compounds on melanoma cells (MEWO) and fibroblasts (HFF) as well as to determine which compound shows the best effect. The MTT assay showed that 18C-M had the biggest effect on reducing cell proliferation, while AMIDO-MET had no effect on proliferation. The localization of porphyrins in cells was monitored by fluorescence microscope and it was found that compounds 10C-M, 14C-M and 18C-M entered the cells and accumulated in cytoplasm. According to the intensity of red staining, it was found that 18C-M accumulates the most. Due to the longest side chain and the highest lipophilicity, it is proven that 18C-M is the most effective photosensitizer. Also, it is proven that all components are equally effective in conditions under and without hypoxia and they did not show dark toxicity.
Keywords
melanom
fotodinamička terapija
fotosenzibilizator
metilirani porfirini
lipofilnost
Keywords (english)
melanoma
photodynamic therapy
photosensitizer
methylated porphyrins
lipophilicity
Language croatian URN:NBN urn:nbn:hr:193:409026 Study programme Title: Drug research and development Type of resource Text File origin Born digital Access conditions Access restricted to students and staff of home institution Terms of use Created on 2020-09-22 15:33:54
