Erkan YURTCU, Yeşim KORKMAZ KASAP, Nur ERDEN ARMUTCUOĞLU

Genistein ve STI571’in (Imatinib) Kronik Myeloblastik Lösemide Etkili Sinyal Protein Düzeylerine Etkileri

Amaç: Kronik myeloid lösemi (KML) malign klonal hematopoetik bir hastalıktır.BCR-ABL1 füzyon geni olup KML’nin moleküler patogenezinde rol oynar. Buprotein bir tirozin kinaz kodlar. AKT, ERK, STAT yolakları üzerinde etkili olan butirozin kinazın modülatörleri GAB2 ve GRB2’dir. KML tedavi protokolünde yeralan STI571 (imatinib mesilat) tirozin kinaz inhibitörüdür. Genistein, östrojeniközeliğinin yanı sıra tirozin kinaz inhibitör aktivitesine sahip olan bitkisel birflavonoiddir. Bu çalışmada, insan KML hücre dizisi K562 hücrelerine STI571uygulaması ile birlikte genistein uygulamasının hücre içi sinyal yolakları üzerineetkisinin protein seviyesinde belirlenmesi hedeflenmiştir.Yöntem: K562 hücreleri standart koşullarda çoğaltıldı. STI571 ve genisteininsitotoksik dozu MTT testi ile belirlendi. STI571 ve genistein, tek tek ve birlikteolacak şekilde 24 ve 48 saat sürelerle uygulandı. Protein düzeyleri ELISAmetoduyla belirlendi. Sonuçlar istatiksel olarak değerlendirildi.Bulgular: Veriler toplu halde değerlendirildiğinde STI571 ve genisteinin tekbaşına ya da birlikte uygulanması ile protein düzeylerinde anlamlı birdeğişikliğe neden olmadığı belirlendi.Sonuç: Bu çalışmada genisteinin STI571 ile birlikte etkileri geniş bir proteinpaneli üzerinde değerlendirilmiştir. STI571’in ve genisteinin tirozin kinazinhibitörü özellikleri bilinmektedir. Ancak her iki ajanın protein düzeyleriüzerine etkilerini inceleyen çalışmalarda tartışmalı sonuçlar mevcuttur.Sonuçlarımıza göre her iki ajanın birlikte kullanılması protein düzeyleriaçısından anlamlı bir fark oluşturmamaktadır.

The Effects of Genistein and STI571 (Imatınıb) on Signal Protein Levels Affecting Chronic Myeloid Leukemia

Objective: Chronic myeloid leukemia (CML) is a malign clonal hematopoietic disease. BCR-ABL1 is a fusion gene and plays role on molecular pathogenesis of CML. This protein encodes a tyrosine kinase. GAB2 and GRB2 are its modulators of this tyrosine kinase which has effects on AKT, ERK, STAT pathways. STI571 (imatinib mesilat) which is used for CML treatment, is a tyrosine kinase inhibitor. Genistein is a herbal flavonoid which has estrogenic effects besides tyrosine kinase inhibitor activity. In this study, we aimed to determine the effect of STI571 and genistein application for intercellular signal transduction pathways at protein level on the K562 cells. Methods: K562 cells were cultured at standard conditions. The cytotoxic concentrations of STI571 and genistein were determined with MTT. STI571 and genistein were applied alone and in combination at 24 and 48 hours. The protein levels were determined by ELISA method. The data were evaluated statistically. Results: There was no statistically significant difference of protein levels with STI571 and genistein alone and in combination. Conclusion: In this study, the effects of STI571 and genistein were evaluated on a wide protein panel. It is well known STI571 and genistein have tyrosine kinase inhibitory effects. However, in previous reports there are controversial results on the protein levels of both agents. Our results showed that the combination of STI571and genistein have no significant effect on the protein levels.

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