Tarantula cubensis alkolik ekstraktının deneysel kolon kanserinde tümör yolakları üzerine etkilerinin moleküler yöntemlerle incelenmesi
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Dosyalar
Tarih
2021
Yazarlar
Dergi Başlığı
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Cilt Başlığı
Yayıncı
Selçuk Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Kolorektal kanser (KRK), kalın bağırsağın bölümleri olan kolon ve rektumun kanseri olarak tanımlanır. KRK küresel ölçekte en fazla morbidite ve mortaliye sebep olan kanserlerden biri olarak bilinmektedir. Günümüzde sistemik olarak herhangi bir yan etkisi ve toksititeye sebebiyet vermeyen, tümör büyümesi ve gelişimini inhibe edebilen kemopreventif bir takım ajanların geliştirilmesi önemli bir araştırma konusu haline gelmektedir. Tarantula cubensisin alkolik ekstraktı (TCAE) veteriner sahada homeopatik ürün olarak son zamanlarda kangren, septisemi, toksemi gibi durumlarda sıklıkla kullanılmaktadır. Sığır kutanöz papillomatozis, köpek oral papillomatozis, köpek meme tümörleri gibi tümörlerin tedavisinde başarılı bir şekilde kullanıldığı bildirilmiştir. Ayrıca serbest oksijen radikallerini azalttığı ve invitro olarak kaspaz-3 yolağını indükleyerek apoptozu aktive edebileceği bildirilmiştir. Bu çalışmanın amacı ratlarda azoksimetan ile indüklenen KRK'de TCAE'nın tümör gelişim yolakları üzerine etkilerini moleküler düzeyde belirlemektir. Bu çalışmada materyal olarak daha önce yapılan bir çalışmanın (Er ve ark 2019) bağırsak parafin blokları kullanıldı. Çalışmada sağlıklı kontrok (SK), Kanser Kontrol (KK), Kanser + Tarantula cubensisin alkolik ekstrat (K-TCAE) gruplarında, her gruptan 6 adet olmak üzere 18 adet parafine gömülü bağırsak dokusu kullanıldı. Elde edilen parafin bloklarından 5 mikron kalınlığında kesitler alınarak Hematoksilen-Eozin ile boyandı. Histopatolojik incelemede Aberrant Crypt Fosi oluşturan kript sayısı ve kriptlerdeki displazi dereceleri skorlandı. Her parafin bloktan alınan örneklere β-catenin, KRAS, APC ve P53 ekspresyonlarını belirlemek için Real Time PCR analizi yapıldı. Aberrant Crypt Fosi (ACF) oluşturan kript sayısı ile kriplerdeki displazinin varlığı ve derecelendirilmesi yönünden K-TCAE grubunda, KK grubuna kıyasla skorlar önemli ölçüde azaldı (P<0.05). Real Time PCR analizinde p53 (P>0.05) ve APC (P<0.001) geninin mRNA ekspresyon düzeylerinin, K-TCAE grubunda arttığı bulundu. KRAS (P<0.05) ve β-catenin (P<0.05) mRNA ekspresyon düzeylerinin K-TCAE grubunda önemli derecede azaldığı saptandı. Sonuç olarak sıçanlarda azoksimetan ile indüklenen KRK'de, TCAE'nın etkileri moleküler olarak değerlendirilmiş olup, deneysel KRK modellerinde KRAS, APC ve β-CATENİN yolaklarında belirgin değişiklikler olduğu ve antitümöral tedavilerde bu yolaklardaki değişimlerin değerlendirme kriteri olarak kullanılabileceği kanısına varıldı.
Colorectal cancer is defined as cancer of the colon and rectum, which are parts of the large intestine. KRK is known to be one of the cancers that cause the highest morbidity and mortality on a global scale. Today, any systemic side effects and toxicity which does not cause the development of some chemopreventive agents capable of inhibiting tumor growth and development is becoming an important research subject. Tarantula cubensis alcoholic extract (TCAE) has been frequently used as a homeopathic product in the veterinary field in cases such as gangrene, septicemia, and toxemia. It has been reported to be used successfully in the treatment of tumors such as bovine cutaneous papillomatosis, canine oral papillomatosis, canine mammary tumors. It has also been reported that it reduces free oxygen radicals and can activate apoptosis by inducing the caspase-3 pathway in vitro. The aim of this study was to determine the effects of Theranecron on tumor development pathways at the molecular level in Azoxymethane-induced KRK in rats. In this study, intestinal paraffin blocks of a previous study (Er et al. 2019) were used as material. In the study, 18 paraffin-embedded intestinal tissues, 6 from each group, were used in healthy control (SK), Cancer Control (KK), Cancer+TCAE (K-TCAE) groups. Sections of 5 micron thickness were taken from the obtained paraffin blocks and stained with Hematoxylin-Eosin. In the histopathological examination, the number of crypts forming ACF and the degree of dysplasia in the crypts were scored. Real Time PCR analysis was performed to determine β-catenin, KRAS, APC and P53 expressions on samples from each paraffin block. In terms of the number of crypts forming ACF and the presence and grading of dysplasia in the crypts, the scores were significantly lower in the K-TCAE group compared to the KK group (P<0.05). In Real Time PCR analysis, mRNA expression levels of p53 (P>0.05) and APC (P<0.001) genes were found to be increased in the K-TCAE group. KRAS (P<0.05) and β-catenin (P<0.05) mRNA expression levels were found to be decreased in the K-TCAE group. As a result, the effects of TCAE in AOM-induced KRK in rats were evaluated molecularly, and it was revealed that there are significant changes in the KRAS, APC and β-catenin pathways in experimental KRK models, and changes in these pathways can be used as evaluation criteria in antitumoral treatments.
Colorectal cancer is defined as cancer of the colon and rectum, which are parts of the large intestine. KRK is known to be one of the cancers that cause the highest morbidity and mortality on a global scale. Today, any systemic side effects and toxicity which does not cause the development of some chemopreventive agents capable of inhibiting tumor growth and development is becoming an important research subject. Tarantula cubensis alcoholic extract (TCAE) has been frequently used as a homeopathic product in the veterinary field in cases such as gangrene, septicemia, and toxemia. It has been reported to be used successfully in the treatment of tumors such as bovine cutaneous papillomatosis, canine oral papillomatosis, canine mammary tumors. It has also been reported that it reduces free oxygen radicals and can activate apoptosis by inducing the caspase-3 pathway in vitro. The aim of this study was to determine the effects of Theranecron on tumor development pathways at the molecular level in Azoxymethane-induced KRK in rats. In this study, intestinal paraffin blocks of a previous study (Er et al. 2019) were used as material. In the study, 18 paraffin-embedded intestinal tissues, 6 from each group, were used in healthy control (SK), Cancer Control (KK), Cancer+TCAE (K-TCAE) groups. Sections of 5 micron thickness were taken from the obtained paraffin blocks and stained with Hematoxylin-Eosin. In the histopathological examination, the number of crypts forming ACF and the degree of dysplasia in the crypts were scored. Real Time PCR analysis was performed to determine β-catenin, KRAS, APC and P53 expressions on samples from each paraffin block. In terms of the number of crypts forming ACF and the presence and grading of dysplasia in the crypts, the scores were significantly lower in the K-TCAE group compared to the KK group (P<0.05). In Real Time PCR analysis, mRNA expression levels of p53 (P>0.05) and APC (P<0.001) genes were found to be increased in the K-TCAE group. KRAS (P<0.05) and β-catenin (P<0.05) mRNA expression levels were found to be decreased in the K-TCAE group. As a result, the effects of TCAE in AOM-induced KRK in rats were evaluated molecularly, and it was revealed that there are significant changes in the KRAS, APC and β-catenin pathways in experimental KRK models, and changes in these pathways can be used as evaluation criteria in antitumoral treatments.
Açıklama
Anahtar Kelimeler
APC, Kolorektal kanser, Colorectal cancer
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Akçakavak, G. (2021). Tarantula Cubensis Alkolik Ekstraktının Deneysel Kolon Kanserinde Tümör Yolakları Üzerine Etkilerinin Moleküler Yöntemlerle İncelenmesi. (Doktora Tezi). Selçuk Üniversitesi, Sağlık Bilimleri Enstitüsü, Konya.
