İNSAN MULTİPLE MYELOMA HÜCRE DİZİSİ ARH77’DE VİNKRİSTİNİN SURVİVİN GEN İFADESİ ÜZERİNE ETKİSİ

Amac: Apoptozis Inhibitor Gen ailesinin (IAP) bir uyesi olan survivin, hucre bolunmesi, apoptozis ve strese hucresel yanit gibi bircok olayda rol oynayan mitotik bir proteindir. Multiple myelomada (MM) temel kemoterapi ajanlarindan biri olan vinkristin, hucrelerde mikrotubul olusumunu engelleyerek apoptozisi uyarmaktadir. Bu calismada, MM hucre dizisi ARH77 hucrelerinde vinkristinin doz ve sure bagimli olarak uygulanmasi ile survivin gen ifadesi uzerinde olusturabilecegi degisiklikleri incelemeyi amacladik. Gerec ve Yontem: Insan MM hucre dizisi ARH77 standart kultur kosullari altinda degisen konsantrasyonlarda (10-7- 10-10 M) ve degisen surelerde (24, 48, 72 ve 96 saat) vinkristine maruz birakildi. Survivin gen ifadesi kantitatif RT-PCR ile belirlendi. Istatistiksel olarak gruplar arasi farklar iki oran z testi ile degerlendirildi. Bulgular: 24 ve 96 saat uygulama ile survivin gen ifadesinde artis belirlenmedi. 48 ve 72 saatlik uygulama sonrasi gorulen gen ifade artisi istatiksel acidan anlamli idi. (p<0,05) Sonuc: Vinkristin uygulanan hucrelerde, survivin gen ifadesine etkisi doza ve sureye bagimlidir. Vinkristinin uyardigi survivin asiri ifadesine bagli olarak hucrelerde meydana gelecek degisiklikleri molekuler duzeyde inceleyen daha detayli calismalara ihtiyac vardir. Anahtar Kelimeler: Survivin, ARH77, Vinkristin. VINCRISTINE INDUCED SURVIVIN EXPRESSION IN THE HUMAN MULTIPLE MYELOMA CELL LINE ARH77 Purpose: Survivin, an inhibitor of the apoptosis (IAP) gene family, is a mitotic protein with actions on various cellular events such as cell division, apoptosis, and cellular response to stress. Vincristine, a chemotherapeutic agent used in multiple myeloma (MM), induces apoptosis via inhibition of spindle formation. We aimed to detect the expression pattern of survivin in vincristine treated MM cell line ARH77. Materials and Methods: Vincristine was added to human multiple myeloma cell line ARH77 cultures for 24, 48, 72, and 96 h and 10-7 to 10-10 M concentrations. Survivin expression was determined by quantitative RT-PCR. Statistical comparisons of ratios were made with two proportions z test. Results: We did not observe an increase in survivin expression after 24 or 96 h of treatment. Survivin expression significantly increased after 48 and 72 h (p<0,05) Conclusion: Expression of survivin in vincristine treated cells is dependent on time and concentration. Detailed studies are needed to evaluate changes in vincristine induced survivin overexpression in cells at the molecular level. Key words: Survivin, ARH77, Vincristine.