Kolon kanseri tedavisi için yeni nanoterapötik modalitelerin geliştirilmesi
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Dosyalar
Tarih
2021
Yazarlar
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Yayıncı
Trakya Üniversitesi Fen Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Bu tez Dr. Dıbırdık ve talebelerinin antikanser aktviteye sahip yeni kimyasal yapılar keşfine yönelik çalışmaları sırasında HT-29 insan kolon kanser modeli üzerinde etkili etnofarmakolojik bir ürünü keşfetmeleri üzerine kuruludur. Bu çalışmada ürünün majör kimyasal bileşenleri gallik asit, tiyofanoks, sülfisomidin, trifenilfosfit, nadolol’ün antiproliferatif etkileri ve kemoterapötikler 5-florourasil, okzaliplatin ve setuksimab ile kombinasyon etkileri incelendi. Takibinde, sinerjistik ilaç kombinasyonlarının nanolipozomal formülasyonları geliştirildi ve antiproliferatif etkileri araştırıldı. Gallik asit HT-29 hücre proliferasyonunu doz-bağımlı baskılamıştır. Tiyofanoks, sülfisomidin, trifenilfosfit ve nadolol’ün antiproliferatif etkileri gözlenmemiştir. Gallik asit’in, 5-florourasil veya okzaliplatin ile kombinasyonu sinerjistik antiproliferatif etki göstermiştir. Gallik asit ve 5-florourasil veya gallik asit ve okzaliplatin kombinasyonları, zaman-bağımlı ve sinerjistik olarak apoptozu indüklemiştir. Gallik asit ve 5-florourasil veya gallik asit ve okzaliplatin kombinasyonlarının nanolipozomal formülasyonları, serbest ilaç formlarından daha fazla antiproliferatif etki göstermiştir. Çalışmamız, gallik asit’in kolon kanseri tedavisinde komplementer ajan olarak 5-florourasil veya okzaliplatin ile kullanılabileceğini gösteren literatürdeki ilk çalışmadır. İkili ilaç yüklü nanolipozomal formülasyonların, kolon kanseri tedavisi için umut vaat eden yeni nanoterapötik formülasyonlar olduğu görülmüştür. Söz konusu in vitro sonuçlar temelinde, in vivo çalışmaların tasarlanıp yürütülmesinin elde edilen sonuçlara önemli katkı sağlaması ve ileriki klinik çalışmalar için de bir temel oluşturması düşünülmektedir.
This thesis is established on the discovery of an ethnopharmacological product that is effective on HT-29 human colon cancer model during Dr. Dıbırdık and his student’s studies to discover new chemical structures with anticancer activity. In this study, the antiproliferative effects of major chemical entities of this product gallic acid, thiofanox, sulfisomidine, triphenylphosphite, nadolol, and their combination with chemotherapeutics 5-fluorouracil, oxaliplatin, and cetuximab were examined. Following, nanoliposomal formulations of synergistic drug combinations were developed and their anti-proliferative effects were investigated. Gallic acid suppressed the HT-29 cell proliferation in a dose-dependent manner. Anti-proliferative effects of thiofanox, sulfisomidine, triphenylphosphite, and nadolol were not observed. Combination of gallic acid with 5-fluorouracil or oxaliplatin showed a synergistic antiproliferative effect. Gallic acid and 5-fluorouracil or gallic acid and oxaliplatin combinations induced apoptosis synergistically and in a time-dependent manner. Nanoliposomal formulations of gallic acid and 5-fluorouracil or gallic acid and oxaliplatin combinations exhibited greater antiproliferative effects than free drug forms. Our study is the first study in the literature showing that gallic acid can be used as a complementary agent in the treatment of colon cancer with 5-fluorouracil or oxaliplatin. Dual drug-loaded nanoliposomal formulations have been shown to be promising new nanotherapeutic formulations for the treatment of colon cancer. Based on these in vitro results, it is thought that the design and execution of in vivo studies will make a significant contribution to the obtained results and may form a basis for future clinical studies.
This thesis is established on the discovery of an ethnopharmacological product that is effective on HT-29 human colon cancer model during Dr. Dıbırdık and his student’s studies to discover new chemical structures with anticancer activity. In this study, the antiproliferative effects of major chemical entities of this product gallic acid, thiofanox, sulfisomidine, triphenylphosphite, nadolol, and their combination with chemotherapeutics 5-fluorouracil, oxaliplatin, and cetuximab were examined. Following, nanoliposomal formulations of synergistic drug combinations were developed and their anti-proliferative effects were investigated. Gallic acid suppressed the HT-29 cell proliferation in a dose-dependent manner. Anti-proliferative effects of thiofanox, sulfisomidine, triphenylphosphite, and nadolol were not observed. Combination of gallic acid with 5-fluorouracil or oxaliplatin showed a synergistic antiproliferative effect. Gallic acid and 5-fluorouracil or gallic acid and oxaliplatin combinations induced apoptosis synergistically and in a time-dependent manner. Nanoliposomal formulations of gallic acid and 5-fluorouracil or gallic acid and oxaliplatin combinations exhibited greater antiproliferative effects than free drug forms. Our study is the first study in the literature showing that gallic acid can be used as a complementary agent in the treatment of colon cancer with 5-fluorouracil or oxaliplatin. Dual drug-loaded nanoliposomal formulations have been shown to be promising new nanotherapeutic formulations for the treatment of colon cancer. Based on these in vitro results, it is thought that the design and execution of in vivo studies will make a significant contribution to the obtained results and may form a basis for future clinical studies.
Açıklama
Anahtar Kelimeler
Kanser, Kemoterapi, İlaç geliştirme, Kombinasyon tedavisi, Ombinasyon indeksi, Hücre proliferasyonu, HT-29 hücre hattı, Nanotıp, Lipozomal nanopartikül, Cancer, Colon adenocarcinoma, Chemotherapy, Combination therapy, Combination index, Cell proliferation, HT-29 cell line, Nanomedicine, Liposomal nanoparticles
