Význam V-ATPasy v rezistenci k cytostatikům a možnosti její inhibice

• Main Author: Belhajová, Marie
• Other Authors: Stiborová, Marie
• Format: Dissertation
• Language: Czech
• Published: 2016
• Online Access: http://www.nusl.cz/ntk/nusl-344142

Cancers belong among the most serious problems of modern medicine and their occurrence is constantly increasing. Neuroblastoma is a malignant embryonal tumor in children, emerging from the peripheral nervous system and is the most frequent tumor in infants. Despite the significant development of therapeutic methods during recent years, this disease remains difficult to treat. It is treated surgically and also with chemotherapy using cytostatic drugs. The cytostatic drugs such as doxorubicin, ellipticine, cisplatin and vincristine have become very significant in treating cancer. However, they induced drug resistance in these neuroblastoma cells. This study investigates expression of the vacuolar H+ -ATPase (V-ATPase), in neuroblastoma cells and its role in the development of drug resistance. V-ATPase is a proton pump required for the acidification of vacuoles, as a sensor of cytosolic pH. A sensitive neuroblastoma cell line (UKF-NB-4) and cells resistant to doxorubicin, ellipticine and cisplatin (UKF-NB-4DOX , UKF-NB-4ELLI , UKF-NB-4CDDP ) were exposed to these agents and the expression of the V-ATPase was studied by Western blot analysis and real-time quantitative reverse tarnscription polymerase chain reaction (RT-PCR). Ellipticine induces an increase in expression of the V-ATPase in neuroblastoma...