Bortezomib ve C vitamini Kombinasyonunun HL-60 Akut Promyelositik Lösemi Hücrelerindeki Etkisinin Değerlendirilmesi

Amaç: C vitamini, tedaviye bağlı yan etkileri azaltma ve kanser hücrelerinin kemoterapötik ajanlara duyarlılığını arttırmak için farklı kanser tedavilerinde kullanılmaktadır. Bunun yanında C vitamininin serbest radikal süpürücü özelliği, inhibitör etkisi ve oksidatif stresi indükleme rolü tedavilerin etkinliğini değiştirebilmektedir. Bu çalışmada lösemi tedavisinde kemoterapötik-sitotoksik ajan olarak kullanılan Bortezomib ve C vitamininin ve bunların kombinasyonlarının HL-60 akut promyelositik lösemi hücrelerindeki etkilerinin araştırılması amaçlandı. Materyal ve Metod: HL-60 hücreleri, Bortezomib (1-100 nM), C vitamini (1-100 µM) konsantrasyonları ve bunların kombinasyonları ile 24 saat ile inkübe edildi. Bortezomib ve C vitamininin monoterapötik ve bunların kombinasyonunun sitotoksik etkileri MTT yöntemiyle, genotoksik etkiler Comet assay yöntemiyle ve intraselüler reaktif oksijen türleri (ROS) düzeyi DCFH-DA floresan prob yöntemiyle analiz edildi. Bulgular: HL-60 hücrelerinde Bortezomib’in konsantrasyonla ilişkili olarak sitotoksik ve genotoksik etkiler oluşturduğu (p˂0.001), C vitaminin ise (100 µM hariç) sitotoksik ve genotoksik etki oluşturmadığı bulundu (p˃0.05). Bortezomib+C vitamini kombinasyonlarında yüksek C vitamini konsantrasyonlarının daha yüksek sitotoksik, genotoksik etkiler oluşturduğu ve hücre içi ROS seviyelerini artırdığı bulundu (p˂0.001). Ancak bu etkiler bortezomib’in monoterapötik etkisi kadar güçlü değildi. Sonuç: HL-60 akut promyelositik lösemi hücrelerinde Bortezomib’in monoterapötik etkilerine karşılık Bortezomib+C vitamini kombinasyonu daha az sitotoksisite, genotoksisite ve hücre içi ROS oluşumuna sebep olmuştur. C vitamininin bu potansiyel etkileri kanser tedavisinde göz önünde bulundurulmalıdır. Bu sonuçların farklı lösemi hücre hatları, in vivo ve preklinik çalışmalarla desteklenmesi lösemi tedavisinde onkolojik etkinliği artırmaya yardımcı olabilir.

Anahtar Kelimeler:

Bortezomib, C vitamini, Sitotoksisite, Genotoksisite, Hücre içi ROS

Evaluation of the Effect of Bortezomib and Vitamin C Combination in HL-60 Acute Promyelocytic Leukemia Cells

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