Nitrik Oksitin Kanser Gelişimi Ve Metastaz Üzerine Etkileri

Year 2017, Volume: 74 Issue: 2, 161 - 174, 01.06.2017

Mehmet Kürşat Derici Emine Demirel Yılmaz

Abstract

Nitrik oksit NO , birçok hücre içi ya da hücreler arası uyarı yolağında görev alan benzersiz bir moleküldür. Farklı kanser hücrelerinde ve dokularında saptanan değişik NO düzeylerinin, farklı düzenleyici etkiler ortaya koyduğu birçok çalışmada gösterilmiştir. Yapısal olarak üretilen NO, kanser hücresi fenotipinin ortaya konmasında önemli rol üstlenmektedir. Bu; kanserin çevre dokulara penetre olmasını, uzak bölgelere yayılmasını ve gelişimi için gerekli olan kaynaklara ulaşabilmesi sağlayacak, en yüksek kan akımını alacağı damarlanma işlevini; kapsamaktadır. Genel olarak, dokuda düşük derişimlerde sentezlenen NO’in etkileri pro-kanseröz olarak değerlendirilebilir. Çok yüksek derişimlerde ise NO, apopitozu, nekrozu uyararak veya anjiyojenezi inhibe ederek, güçlü bir anti-kanser madde olarak görev yapmaktadır. Öte yandan, NO düzeylerindeki artışın, metastaz basamakları üzerine olan etkileri sebebiyle kanserin farklı lokalizasyonlarda büyümesini ve ilerleyişini arttırabildiği ortaya konmuştur. Metastazda NO’in oynadığı rol, hücre tipi, NO derişimi, katılan organlar veya NO’in kanseral sürece katıldığı dönem gibi, farklı faktörlerden etkilenmektedir. NO’in bu çok yönlü ve farklı etkileri, kanserin büyümesini yavaşlatmak ve kemoterapi/radyoterapi etkinliğini arttırmak amacıyla, kanserin birçok preklinik modellerinde kullanılmaktadır. Bu yaklaşımlar yeni anti-kanser stratejileri olarak ön görülmektedir

Keywords

Nitrik oksit, tümör, metastaz

The Effects Of Nıtrıc Oxıde On Cancer Development And Metastasıs

Abstract

Nitric oxide NO is unique molecule involved in many intracellular or intercellular signaling pathways and its importance varies from cell to cell. It is demonstrated that heterogeneous regulating responses to various NO levels have been observed in in different types of tumors. Constitutively expressed NO plays an important role in drawing up the phenotype of tumor cells. The roles of NO in tumor growth cover the tumor penetration into the surrounding tissues to spread to remote areas and the development of the neovascularization to obtain the highest blood flow for the necessary resources. Generally, effects of NO at low concentrations considered as protumoral. In very high concentrations of NO, it serves as a potent anti-tumor agent by inhibiting angiogenesis or inducing apoptosis and/or necrosis. While NOS activation is expected to show anti-tumor effect, it has been demonstrated that NO may increase the progression and propagation of cancer due to the effects on metastasis process. The effect of NO on metastasis is affected by different factors such as cell type, dose, the types of participating organs or the period in which NO involved in the tumor development. These different characteristic effects of NO expression are used therapeutically in many preclinical models of cancer in order to increase the inhibition of tumor growth and chemotherapy/ radiotherapy efficiency. These approaches are envisaged as new anticancer strategies

Keywords

Nitric oxide, neoplasms, metastasis

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