Prostat kanseri hücre terapisinde adiponektin reseptör agonisti ile kombine kemoterapötik etkinliğin araştırılması
Küçük Resim Yok
Tarih
2021
Yazarlar
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Yayıncı
Trakya Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Prostat kanseri, başta sanayileşmiş ülkelerde erkekler arasında en sık tanı konulan kanserlerden biri olup toplam erkek kanser mortalitesinin %6,6'sını oluşturur. Her ne kadar tedavide androjen ablasyon terapisi, cerrahi müdahale, kemoterapi, radyoterapi veya immünoterapi uygulansa da birçok olguda sonuçlar yaşa, ilişkili sağlık sorunlarına, tümör histolojisine ve kanserin boyutuna göre değişkenlik gösterir. Bu nedenle, daha etkin ve yan etkileri düşük yeni moleküllerin sentezi veya bunların başka moleküller ile kombine edilerek kullanılması gibi yeni tedavi stratejilerine ihtiyaç vardır. Obezite günümüzde önemli bir sağlık sorunu haline gelmiş ve küresel hastalık yükü salgın boyutlara ulaşmıştır. Adiponektin, anti-diyabetik ve anti-proliferatif özelliklere sahip, yağ dokusu kaynaklı bir adipokindir. Plazma adiponektin seviyeleri obez bireylerde azalır ve bu özellik çeşitli metabolik, immünolojik ve neoplastik hastalıkların gelişimi ile yakından ilişkilidir. Son çalışmalara göre prostat kanseri hastalarında serum adiponektin seviyeleri düşüktür ve tümör dokularında adiponektin reseptörlerinin ekspresyonu azdır. Bu çalışmada, adiponektin reseptör agonisti adiporon molekülünün insan prostat kanser hücreleri üzerindeki etkileri ile adiporonun kemoterapi ajanı dosetaksel ile kombine uygulamasının etkinliği analiz edildi. Araştırmada, adiporon, dosetaksel veya kombinasyonları kastrasyona dirençli PC3 hücrelerine uygulanarak 72 saat inkübe edildi. Yapılan uygulamaların hücrelerin sağkalımı, hücre döngüsü, apoptoz ve migrasyonuna etkileri MTT, sitometrik, yara iyileşmesi ve RT-qPCR yöntemleri ile değerlendirildi. Elde edilen verilere göre adiporon ve dosetaksel, hücrelerin sağkalımını konsantrasyona bağlı olarak azalttı. Hücrelerin 12,5 ?M adiporon, 2,5 nM dosetaksel veya ikisinin kombinasyonuna maruz bırakılması, hücre sağkalımını ayrı tedaviye göre sinerjik etki ile düşürdü. Bu etkide, hücre döngüsünün G1 fazında tutulması, artan non-apoptotik hücre ölümleri ile apoptozun uyarılmasının rol oynadığı saptandı. Her iki ajan da hücre göçünü belirgin düzeyde inhibe ederken, kombine tedavi migrasyon hızını tek tedaviye göre daha fazla baskıladı. Bu tez çalışmasından elde edilen verilere göre, adiponektin reseptör agonisti adiporonun ayrı veya dosetaksel ile kombine uygulanması insan kastrasyon dirençli prostat kanserinin tedavisinde yer bulabilir. Bununla birlikte bu molekülün klinikte yer bulup bulamayacağı in vivo preklinik çalışmalar ile desteklenmesi önerilir.
Prostate cancer is one of the most frequently diagnosed cancers among men in industrialized countries, accounting for 6.6% of total male cancer mortality. Despite the use of androgen ablation therapy, surgical intervention, chemotherapy, radiotherapy, or immunotherapy, in most cases results depend on age-related health issues, tumor histology, and the extent of the cancer. Therefore, there is a need for new treatment strategies, such as developing new molecules that are more effective and with low side effects or using them in combination with other molecules. Obesity is a rising obstacle today and the global disease burden has reached epidemic proportions. Adiponectin is an adipocyte derived adipose tissue with anti-diabetic and anti-proliferative properties. Plasma adiponectin levels decrease in obese individuals and this factor is closely related to the development of various metabolic, immunological, and neoplastic diseases. According to recent studies, serum adiponectin levels are low in prostate cancer patients and less expression of adiponectin receptors in tumor tissues. In the present study, effects of the adiponectin receptor agonist adiporon molecule on human prostate cancer cells and the efficacy of combining adiporon with the chemotherapy agent docetaxel were investigated. In the study, adiporon, docetaxel or their combination was administered to castration resistant PC3 cells, and incubated for 72 hours. The effects of the applications on cell survival, cell cycle, apoptosis and migration were evaluated using MTT, cytometric, wound healing and RT-qPCR methods. According to the data obtained, adiporon and docetaxel decreased the survival of cells depending on the concentration. Exposing the cells to 12.5 ?M adiporon, 2.5 nM docetaxel, or a combination of the two, decreased cell survival with a synergistic effect over the separate treatment. It was determined that arresiting the cell cycle in the G1 phase, increasing non-apoptotic cell death and the induction of apoptosis played a role in this effect. While both agents significantly inhibited cell migration, combined therapy suppressed migration rate more than a single treatment. According to the data obtained from this thesis, the administration of adiponectin receptor agonist adiporon alone or in combination with docetaxel may find a place in the treatment of human castration resistant prostate cancer. However, whether this molecule will find a place in the clinic or not, it is recommended to support in vivo preclinical studies.
Prostate cancer is one of the most frequently diagnosed cancers among men in industrialized countries, accounting for 6.6% of total male cancer mortality. Despite the use of androgen ablation therapy, surgical intervention, chemotherapy, radiotherapy, or immunotherapy, in most cases results depend on age-related health issues, tumor histology, and the extent of the cancer. Therefore, there is a need for new treatment strategies, such as developing new molecules that are more effective and with low side effects or using them in combination with other molecules. Obesity is a rising obstacle today and the global disease burden has reached epidemic proportions. Adiponectin is an adipocyte derived adipose tissue with anti-diabetic and anti-proliferative properties. Plasma adiponectin levels decrease in obese individuals and this factor is closely related to the development of various metabolic, immunological, and neoplastic diseases. According to recent studies, serum adiponectin levels are low in prostate cancer patients and less expression of adiponectin receptors in tumor tissues. In the present study, effects of the adiponectin receptor agonist adiporon molecule on human prostate cancer cells and the efficacy of combining adiporon with the chemotherapy agent docetaxel were investigated. In the study, adiporon, docetaxel or their combination was administered to castration resistant PC3 cells, and incubated for 72 hours. The effects of the applications on cell survival, cell cycle, apoptosis and migration were evaluated using MTT, cytometric, wound healing and RT-qPCR methods. According to the data obtained, adiporon and docetaxel decreased the survival of cells depending on the concentration. Exposing the cells to 12.5 ?M adiporon, 2.5 nM docetaxel, or a combination of the two, decreased cell survival with a synergistic effect over the separate treatment. It was determined that arresiting the cell cycle in the G1 phase, increasing non-apoptotic cell death and the induction of apoptosis played a role in this effect. While both agents significantly inhibited cell migration, combined therapy suppressed migration rate more than a single treatment. According to the data obtained from this thesis, the administration of adiponectin receptor agonist adiporon alone or in combination with docetaxel may find a place in the treatment of human castration resistant prostate cancer. However, whether this molecule will find a place in the clinic or not, it is recommended to support in vivo preclinical studies.
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Anahtar Kelimeler
Biyoteknoloji, Biotechnology ; Tıbbi Biyoloji
