4T1 Meme Kanseri Fare Modelinde MMH-1’in Anti-Kanser Etkisinin Araştırılması
Yükleniyor...
Dosyalar
Tarih
2022
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Kanser hücrelerinin büyüyüp gelişmesine, hayatta kalmasına, invazyonuna
ve metastazına CA IX enziminin destekleyici rolleri bulunur. Sülfonamidlerin bu enzim
üzerine inhibitör etki gösterdiği ve kanser tedavisine katkı sağlayabileceği
bildirilmektedir. Bu çalışmada sülfonamid türevi olan MMH-1 maddesinin hem in vitro
hem de in vivo ortamda meme kanseri üzerine olan etkisini sitotoksik, metabolik ve
moleküler düzeyde açıklamayı amaçladık.
Materyal ve Metot: CA IX üzerine MMH-1’in inhibitör etkisi Moleküler
Docking yöntemiyle incelendikten sonra çalışmanın in vitro kısmına geçildi. 4T1
hücreleri üzerine MMH-1’in sitotoksik etkileri MTT yöntemi belirlendi. Apoptotik
etkileri AO/EtBr boyama ve Annexin-V ile flow sitometrik olarak analiz edildi. İn vivo
kısmında tümör dokularında CA IX, Vimentin, E-Cadherin ve Kaspaz 3’ün hem protein
hem de gen ekspresyonları analiz edildi ve histopatolojik inceleme yapıldı. Ayrıca kan
numuneleri ile de metabolomik analiz gerçekleştirildi.
Bulgular: Moleküler Docking sonuçları MMH-1’in CA IX ile bağlanma afinitesi
ve modlarına sahip olduğunu gösterdi. MMH-1’in in vitro ve in vivo şartlarda apoptozu
tetiklediği görüldü. Tümör hacimlerinin azalmasında ve kanser hücrelerinin ölümünde
MMH-1’in etkili olduğunu histopatolojik sonuçlar da destekledi. Ayrıca kanserin neden
olduğu metabolomik değişimlerin azalmasında da başarılı sonuçlar gösterdi.
Sonuç: Bu bulgular MMH-1 maddesinin CA IX üzerine inhibitör etkisi olduğunu
ve apoptozu tetikleyerek kanser hücrelerini öldürdüğünü gösterdi. MMH-1’in farklı
dozları ve farklı kemoterapötik ajanlarla kombine kullanımı meme kanseri tedavisinde
potansiyel bir terapötik aday olarak kullanılabileceğini düşünüyoruz.
Anahtar Kelimeler: Apoptoz, Meme Kanseri, MMH-1, Sülfonamid, Kanser
Modeli
Aim: CA IX enzyme has supportive roles in the growth, development, survival, invasion and metastasis of cancer cells. Sulfonamides have an inhibitory effect on this enzyme and may contribute to cancer treatment. In this study, we aimed to explain the effect of MMH-1, a sulfonamide derivative, on breast cancer both in vitro and in vivo, in cytotoxic, metabolic and molecular levels. Material and Method: After examining the inhibitory effect of MMH-1 on CA IX with Molecular Docking, in vitro part of the study was started. The cytotoxic effects of MMH-1 on 4T1 cells were determined by the MTT. Apoptotic effects were analyzed by AO/EtBr staining and Annexin-V. In the in vivo part, both protein and gene expressions of CA IX, Vimentin, E-Cadherin and Caspase 3 in tumor tissues were analyzed and histopathological examination was performed. Also, metabolomic analysis was performed with blood samples. Results: Molecular Docking results showed that MMH-1 has binding affinity and modes with CA IX. It was observed that MMH-1 triggered apoptosis in vitro and in vivo. Histopathological results also supported that MMH-1 was effective in the reduction of tumor volumes and the death of cancer cells. It also showed successful results in reducing the metabolomic changes caused by cancer. Conclusion: These findigs showed that MMH-1 has an inhibitory effect on CA IX and kills cancer cells by triggering apoptosis. Different doses of MMH-1 and its combined use with different chemotherapeutic agents can be used as potential therapeutic candidate in the treatment of breast cancer. Keywords: Apoptosis, Breast Cancer, Cancer Model, MMH-1, Sulfonamide
Aim: CA IX enzyme has supportive roles in the growth, development, survival, invasion and metastasis of cancer cells. Sulfonamides have an inhibitory effect on this enzyme and may contribute to cancer treatment. In this study, we aimed to explain the effect of MMH-1, a sulfonamide derivative, on breast cancer both in vitro and in vivo, in cytotoxic, metabolic and molecular levels. Material and Method: After examining the inhibitory effect of MMH-1 on CA IX with Molecular Docking, in vitro part of the study was started. The cytotoxic effects of MMH-1 on 4T1 cells were determined by the MTT. Apoptotic effects were analyzed by AO/EtBr staining and Annexin-V. In the in vivo part, both protein and gene expressions of CA IX, Vimentin, E-Cadherin and Caspase 3 in tumor tissues were analyzed and histopathological examination was performed. Also, metabolomic analysis was performed with blood samples. Results: Molecular Docking results showed that MMH-1 has binding affinity and modes with CA IX. It was observed that MMH-1 triggered apoptosis in vitro and in vivo. Histopathological results also supported that MMH-1 was effective in the reduction of tumor volumes and the death of cancer cells. It also showed successful results in reducing the metabolomic changes caused by cancer. Conclusion: These findigs showed that MMH-1 has an inhibitory effect on CA IX and kills cancer cells by triggering apoptosis. Different doses of MMH-1 and its combined use with different chemotherapeutic agents can be used as potential therapeutic candidate in the treatment of breast cancer. Keywords: Apoptosis, Breast Cancer, Cancer Model, MMH-1, Sulfonamide
Açıklama
Anahtar Kelimeler
Apoptoz, Meme Kanseri, MMH-1, Sülfonamid, Kanser Modeli
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Akmeşe, Ş. (2022). 4T1 Meme Kanseri Fare Modelinde MMH-1’in
Anti-Kanser Etkisinin Araştırılması. Doktora Tezi, İnönü Üniversitesi.
