Nöroblastom Hücre Hattı Üzerinde (SH SY- 5Y) Kemoteröpatik İlaç Tedavisine Cape Katkısının İnflamatuvar Sürece Etkilerinin İn Vitro Araştırılması

Abstract

In Vitro Investigation of the Effects of Cape Contribution to Chemotherapeutic Drug Treatment on the Neuroblastoma Cell Line (SH SY- 5Y) on the Inflammatory Process

Abstract

Nöroblastom pediatrik grupta yüksek riskli hastalarda çoklu tedavilere cevapsız kalan ve 5 yıllık sağkalım oranı %50’den düşük olan sempatik sinir sistemi tümörüdür. Tedavi protokollerinde evrelerine göre kemoterapi, radyoterapi, cerrahi kullanılsa da bu tedavilerin komplikasyonları ve toksik etkileri de mortaliteyi artıran sebepler arasında bulunmaktadır. Topotekan nöroblastom tedavisinde aktif olarak kullanılmaktadır. Sağ kalım süresini artırıcı etkisi olsa da toksik etkileri nedeni ile kullanımı sınırlanmaktadır. Bu sebeplerle nöroblastom, tedavide yeni yaklaşımlara ve mevcut tedavilerin komplikasyonlarını azaltacak ajanlara ihtiyacı olan bir hastalıktır. CAPE antienflamatuar, immünomodülatör, antioksidan ve antikanser özellikleri bilinen ve özellikle kanser hücrelerini seçici olarak etkilemesi ile tercih edilen doğal bir bileşiktir. Kanser tedavisi sırasında inflamatuar mikroçevrenin düzenlenmesi tedavi planında önem arzetmektedir. Enflamasyon hem pro- hem de anti-tümör özelliklere sahip düzenleyici bir sistemdir. Bu bilgiler doğrultusunda çalışmamızda SHSY-5Y NB hücre hattında Topotekan ve CAPE tedavilerinin enflamatuar sürece etkilerini IL-1α, IL-6, IL-18 ve VEGF antikorları ile apoptotik sürece etkilerini de TUNEL yöntemini kullanarak karşılaştırmayı amaçladık. Çalışmamızda SH-SY5Y nöroblastom hücre hattı kullanıldı. Hücreler çoğaltıldıktan sonra ICC ve Tunel Boyamaları için ayrı ayrı iki grup oluşturuldu. Her bir grup kendi içinde dörde ayrılarak 1. ve 2. gruplara Topotekan ve CAPE ayrı ayrı, 3. gruba Topotekan ve CAPE birlikte verildi, 4. gruba herhangi bir madde verilmeyerek etken maddelere 24 saat boyunca maruz bırakıldı. Ardından ICC ve TUNEL metodları ile boyama işlemleri yapıldı. Elde edilen bulgularda CAPE+Topotekan uygulanan grupta belirgin olmak üzere CAPE ve Topotekan uygulanan gruplarda IL-1α, IL-6, IL-18 ve VEGF boyanma şiddetleri artmış olarak bulundu. TUNEL boyaması ile yapılan değerlendirmede ise en fazla apoptotik hücre CAPE uygulanan grupta görülmekle beraber Topotekan ve CAPE+Topotekan uygulanan gruplarda da apoptosis artışı saptandı. Çalışmamızın sonuçları SH-SY5Y nöroblastom hücrelerinde CAPE ve Topotekanın inflamasyonu şiddetlendirerek apoptosisi tetiklediğini, CAPE grubunda daha fazla apoptotik hücre görülmesinin Topotekana göre bu hücrelerde daha sitotoksik etkili olduğunu, beraber kullanıldığında ise CAPE’nin Topotekana sinerjistik etkili olduğunu göstermiştir. Anahtar Kelimeler: Apoptosis, CAPE, İnflamasyon, SHSY-5Y, Topotekan

Keywords

• Apoptosis
• CAPE
• Mediators of Inflammation

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