Akademik Veri Yönetim Sistemi
TURKIYE KLINIKLERI TIP BILIMLERI DERGISI, cilt.31, sa.5, ss.1087-1093, 2011 (SCI-Expanded)
Objective: Some of the cytotoxic agents used in treatment of neuroblastoma show their effects via apoptosis mechanisms. Apoptosis mechanisms and drug interactions are currently studied topics. Bcl-2 is an inhibitor of apoptosis in intrinsic pathway. Bax is a member of Bcl-2 protein family and acts as an apoptosis agonist. Fas is a transmembrane protein and stimulates apoptosis in extrinsic pathway. Survivin, which is a member of apoptosis inhibitor protein family, prevents apoptosis by directly inhibiting caspase 3 and caspase 7. The aim of this study is to investigate the interaction of apoptosis-related proteins with chemotherapeutic agents in neuroblastoma cell culture line. Material and Methods: Retinoic acid and cytotoxic agents and combinations of these (cisplatin, vincristine, cyclophosphamide, etoposide, doxorubicin) were applied into 96-well culture plates in LD50 optimized doses. Expressions of Fas, Bcl-2, Bax and survivin, which are among apoptosis-related proteins were determined immunohistochemically. Results: While neuroblastoma cells of control group to which medication was not administered were Fas negative, varying levels of Fat expression was detected in retinoic, cytotoxic agent and combination administered groups. While Bcl-2 was predominantly positive in the control group, it was negative in ciaplatin, etoposide, retinoic acid-cisplatin combination groups. While Bax was negative in control group, it was predominantly positive in retinoic acid, retinoic acid- etoposide, retinoic acid, doxorubicin combinations. While survivin was negative in control group, it was positive in retinoic acid, cisplatin, retinoic acid-cytotoxic agent combinations. Conclusion: Extrinsic pathyway promoter Fat expression appeared after administration of cytotoxic agents and retinoic acid showing their effects via apoptosis. On the other hand, in intrinsic pathway, decrease in anti-apoptotic Bcl-2 expression with administered agents and increase in apoptosis agonist Bax expression especially with retinoic acid and some combinations of it were remarkable. On the other hand, expression of survivin increased which is the inhibitor of caspase common system in which intrinsic and extrinsic pathways come together. In conclusion, it is concluded that further research should be done about the role of antiapoptotic survivin which is located in 17q gain region and known as a poor prognostic criteria in neuroblastoma play a role in chemoresistance.