Deneysel olarak oluşturulmuş meme tümörlerinde rosuvastatinin arginaz enzim aktivitesi, ornitin ve poliamin düzeylerine etkisi
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Dosyalar
Tarih
2013
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Trakya Üniversitesi Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Meme kanseri, dünyada kadınlar arasında en sık görülen malign tümördür. Üre döngüsünün anahtar enzimi olan arginaz, L-argininden üre ve ornitin oluşturmaktadır. Kanserli hastalarda arginaz enzim aktivitesinin arttığı ve arginazın kanserde biyolojik bir belirteç olarak kullanılabileceği bildirilmiştir. Bu çalışmada meme kanseri oluşturulmuş farelerde serumda arginaz enzim aktivitesi, ornitin ve poliamin (putresin, spermidin, spermin) düzeylerine, dokuda ise arginaz enzim aktivitesi, ornitin ve poliamin (putresin, spermidin, spermin) düzeylerine, rosuvastatin'in etkisi araştırılmıştır. Çalışmada 50 tane erkek Balb/c cinsi fare kullanıldı. Farelerin sol ayak iç bölgesine 0.2 mL erhlich asit tümör hücresi enjekte edildi. Fareler sağlıklı kontrol, sağlıklı tedavi, tümör kontrol, tedavi 1 ve tedavi 2 grupları olmak üzere 5 gruba ayrıldı ve kontrol grupları hariç diğer gruplara 1 mg/kg ve ikinci tedavi grubuna 20 mg/kg rosuvastatin 15 gün boyunca intraperitonel olarak verildi. Tümörlü hayvanların serumunda artmış bulunan arginaz enzim aktivitesinin rosuvastatin tedavisi ile birlikte istatistiksel olarak anlamlı şekilde azaldığı gözlendi (p=0.001). Serum poliamin (putresin, spermidin, spermin) düzeylerinin, rosuvastatin tedavisi ile azaldığı saptandı. Doku arginaz enzim aktivitesi ve ornitin düzeyleri tedavi gruplarında tümör grubuna göre anlamlı olarak düşük bulundu (p=0.002). Doku poliamin (putresin, spermidin, spermin) düzeylerinin ise yine rosuvastatin tedavisi ile birlikte azaldığı gözlendi. Sonuç olarak, rosuvastatin?in arginaz enzim aktivitesini inhibe ederek yolağı nitrik oksit sentaz üzerinden nitrik oksit oluşumuna kaydırdığı, bu sayede poliaminlerin öncü maddesi olan ornitin sentezini azalttığı ve nitrik oksit üretimini teşvik ederek kansere karşı koruyucu bir rol oynayabileceği söylenebilir. Kanser tedavisinde umut verici bir ajan olan rosuvastatin'in bu alandaki etkileri daha ileri çalışmalar ve yeni parametreler ile desteklenmelidir.
Abstract
Breast cancer is the most common malignant tumour of women around the world. As a key enzyme of the urea cycle, arginase leads to formation of urea and ornithine from L-arginine. In the patients with several different cancer, arginase has been found to be higher and reported to be a useful biological marker. The aim of this study was to investigate effect of rosuvastatin on serum and cancer tissue arginase enzyme activity, ornithine and polyamine (putrescine, spermidine, spermine) levels. In this study, 50 male Balb/c mice were used. 0.2 ml Erchlich acid tumor cell was injected into the subcutan part of their left foot. The mice were divided into five groups as healty control group, healty treatment, tumour control, treatment 1, treatment 2 groups. 1 mg/kg and 20 mg/kg dose of rosuvastatin were given intraperitonealy. ncreased serum arginase activity was significantly decreased with rosuvastatin treatment (p=0,001). In the tumour tissue, arginase activity and ornithine levels were significantly decreased in treatment groups than tumour group (p=0.002). Tissue polyamine (putresine, spermidine, spermine) levels also decreased with rosuvastatin treatment. As a conclusion, we may suggest that rosuvastatin may have some protective effects on breast cancer development as inhibits arginase enzyme activity and ornithine levels, precursor of polyamines, and therefore inducing NO production via NOS. As a promising anticancer agent, the net effects of rosuvastatin in this mechanism should be supported with more advanced studies and new parameters.
Abstract
Breast cancer is the most common malignant tumour of women around the world. As a key enzyme of the urea cycle, arginase leads to formation of urea and ornithine from L-arginine. In the patients with several different cancer, arginase has been found to be higher and reported to be a useful biological marker. The aim of this study was to investigate effect of rosuvastatin on serum and cancer tissue arginase enzyme activity, ornithine and polyamine (putrescine, spermidine, spermine) levels. In this study, 50 male Balb/c mice were used. 0.2 ml Erchlich acid tumor cell was injected into the subcutan part of their left foot. The mice were divided into five groups as healty control group, healty treatment, tumour control, treatment 1, treatment 2 groups. 1 mg/kg and 20 mg/kg dose of rosuvastatin were given intraperitonealy. ncreased serum arginase activity was significantly decreased with rosuvastatin treatment (p=0,001). In the tumour tissue, arginase activity and ornithine levels were significantly decreased in treatment groups than tumour group (p=0.002). Tissue polyamine (putresine, spermidine, spermine) levels also decreased with rosuvastatin treatment. As a conclusion, we may suggest that rosuvastatin may have some protective effects on breast cancer development as inhibits arginase enzyme activity and ornithine levels, precursor of polyamines, and therefore inducing NO production via NOS. As a promising anticancer agent, the net effects of rosuvastatin in this mechanism should be supported with more advanced studies and new parameters.
Açıklama
Tıpta Uzmanlık Tezi
Anahtar Kelimeler
Meme Kanseri, Rosuvastatin, Poliaminler, Ornitin, Arginaz, Breast Cancer, Polyamines, Ornithine, Arginase
