Over kanseri hücre hattında timokinon ve sisplatinin hücre göçü ve anjiyogenez üzerine etkilerinin araştırılması
Küçük Resim Yok
Tarih
2025
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Düzce Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Over kanseri, kadınlarda sık görülen ve yüksek mortaliteye sahip jinekolojik malignitelerden biridir. Genellikle ileri evrede tanı alması ve platin temelli kemoterapilere karşı gelişen direnç, tedavi etkinliğini sınırlamaktadır. Sisplatin (Cis), over kanserinde yaygın kullanılan bir kemoterapötik ajandır; ancak toksisitesi ve sekonder direnç gelişimi, yeni stratejilere olan ihtiyacı artırmaktadır. Bu bağlamda, doğal biyoaktif bileşiklerin kemoterapi ile kombinasyonu dikkat çeken bir yaklaşımdır. Timokinon (TQ), Nigella sativa'dan elde edilen ve antineoplastik özellikleriyle öne çıkan bir fitokimyasal bileşiktir. Bu tez çalışmasında, TQ, Cis ve kombinasyonlarının SKOV-3 over kanseri hücre hattı üzerindeki etkileri in vitro olarak değerlendirilmiştir. Araştırma, özellikle anjiyogenez ve hücre migrasyonu ile ilişkili moleküler yolları hedef almıştır. TQ (0–1000 µM) ve Cis (0–200 µM) ajanlarının farklı süre ve dozlarda sitotoksik etkileri MTT testi ile analiz edilmiş, ardından VEGF, VEGFR1, MMP-2 ve MMP-9 protein düzeyleri Western blot yöntemiyle değerlendirilmiştir. Tekil ve kombinasyon tedavilerinin hücre canlılığı, morfolojik değişiklikler ve doz-zaman yanıtları detaylı biçimde incelenmiştir. Bulgular, TQ'nun VEGFR1 düzeyini azaltırken yüksek dozlarda MMP-2 ekspresyonunu artırdığını; Cis'in ise VEGFR1 ve MMP-9 düzeylerinde azalmaya yol açtığını göstermiştir. En belirgin etki, kombinasyon uygulamalarında gözlenmiş; VEGFR1, MMP-2 ve MMP-9 düzeylerinin baskılanmasıyla hem anjiyogenez hem migrasyon anlamlı şekilde engellenmiştir. Özellikle 48 saatlik ardışık uygulamalarda TQ ön tedavisinin Cis etkinliğini artırdığı hücrte canlılığı analizleri ile saptanmıştır. Sonuç olarak, bu çalışma TQ ve Cis'in birlikte kullanımının SKOV-3 hücrelerinde sinerjistik antitümöral etkiler gösterebileceğini ve moleküler düzeyde tümör progresyonunu baskılayabileceğini ortaya koymuştur. Bulgular, doğal bileşiklerin kemoterapi ile birlikte kullanımının daha etkili ve seçici tedavi stratejileri geliştirmede önemli bir potansiyel taşıdığını desteklemektedir.
Ovarian cancer is one of the most common gynecological malignancies with high mortality in women. The disease is often diagnosed at an advanced stage, and the development of resistance to platinum-based chemotherapies limits treatment efficacy. Cisplatin (Cis) is a widely used platinum-based chemotherapeutic agent in the treatment of ovarian cancer; however, its systemic toxicity and secondary resistance mechanisms highlight the need for new and more effective therapeutic strategies. In this context, the combination of natural bioactive compounds with chemotherapy has emerged as a promising approach. Thymoquinone (TQ), a major phytochemical compound derived from Nigella sativa, stands out with its anti-neoplastic, anti-inflammatory, and antioxidant properties. In this thesis study, the effects of TQ, Cis, and their combinations on the SKOV-3 ovarian cancer cell line were evaluated in vitro. The research particularly focused on molecular pathways related to angiogenesis and cell migration. The cytotoxic effects of TQ (0–1000 µM) and Cis (0–200 µM) were assessed at different doses and incubation times (24, 48, and 72 hours) using the MTT assay. Subsequently, the protein levels of angiogenesis markers (VEGF and VEGFR1) and invasion/migration markers (MMP-2 and MMP-9) were analyzed via Western blotting. The effects of single and combined treatments on cell viability, morphological alterations, and dose-time responses were comprehensively examined. The findings showed that TQ reduced VEGFR1 expression while increasing MMP-2 levels at higher doses. Cis treatment led to decreased expression of VEGFR1 and MMP-9. The most notable results were obtained with the combination treatments, where VEGFR1, MMP-2, and MMP-9 levels were suppressed, leading to significant inhibition of both angiogenesis and migration. In particular, sequential application for 48 hours revealed that pretreatment with TQ enhanced the cytotoxic effect of Cis, as demonstrated by the viability analysis. In conclusion, this study revealed that the combined use of TQ and Cis may exhibit synergistic antitumor effects on SKOV-3 cells and can suppress tumor progression at the molecular level. These findings support the potential of integrating natural compounds into conventional chemotherapy regimens to develop more effective and selective treatment strategies.
Ovarian cancer is one of the most common gynecological malignancies with high mortality in women. The disease is often diagnosed at an advanced stage, and the development of resistance to platinum-based chemotherapies limits treatment efficacy. Cisplatin (Cis) is a widely used platinum-based chemotherapeutic agent in the treatment of ovarian cancer; however, its systemic toxicity and secondary resistance mechanisms highlight the need for new and more effective therapeutic strategies. In this context, the combination of natural bioactive compounds with chemotherapy has emerged as a promising approach. Thymoquinone (TQ), a major phytochemical compound derived from Nigella sativa, stands out with its anti-neoplastic, anti-inflammatory, and antioxidant properties. In this thesis study, the effects of TQ, Cis, and their combinations on the SKOV-3 ovarian cancer cell line were evaluated in vitro. The research particularly focused on molecular pathways related to angiogenesis and cell migration. The cytotoxic effects of TQ (0–1000 µM) and Cis (0–200 µM) were assessed at different doses and incubation times (24, 48, and 72 hours) using the MTT assay. Subsequently, the protein levels of angiogenesis markers (VEGF and VEGFR1) and invasion/migration markers (MMP-2 and MMP-9) were analyzed via Western blotting. The effects of single and combined treatments on cell viability, morphological alterations, and dose-time responses were comprehensively examined. The findings showed that TQ reduced VEGFR1 expression while increasing MMP-2 levels at higher doses. Cis treatment led to decreased expression of VEGFR1 and MMP-9. The most notable results were obtained with the combination treatments, where VEGFR1, MMP-2, and MMP-9 levels were suppressed, leading to significant inhibition of both angiogenesis and migration. In particular, sequential application for 48 hours revealed that pretreatment with TQ enhanced the cytotoxic effect of Cis, as demonstrated by the viability analysis. In conclusion, this study revealed that the combined use of TQ and Cis may exhibit synergistic antitumor effects on SKOV-3 cells and can suppress tumor progression at the molecular level. These findings support the potential of integrating natural compounds into conventional chemotherapy regimens to develop more effective and selective treatment strategies.
Açıklama
Anahtar Kelimeler
Histoloji ve Embriyoloji, Histology and Embryology
