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The role of V-ATPase in resistence to cytostatics and the possibility of its inhibition
Belhajová, Marie ; Stiborová, Marie (advisor) ; Moserová, Michaela (referee)
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...
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The role of V-ATPase in resistence to cytostatics and the possibility of its inhibition
Belhajová, Marie ; Stiborová, Marie (advisor) ; Moserová, Michaela (referee)
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...
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The Study of the DNA of Tumor Cells Exposed to Doxorubicin
Belhajová, Marie ; Poljaková, Jitka (advisor) ; Mrízová, Iveta (referee)
Cancerous diseases are among the most serious problems of modern medicine and their occurrence is constantly increasing. Despite the significant development of therapeutic methods during recent years, this disease remains difficult to treat. Neuroblastoma (NB) is a malignant embryonal tumor in children, emerging from the peripheral nervous system and is the most frequent tumor in children. It is treated surgically and also with chemotherapy using cytostatic drugs. The cytostatic drug Doxorubicin has become very significant in treating cancer. Doxorubicin is a anticancer medication whose cytotoxic effect is based on a number of mechanisms, one of which is the intercalation into DNA molecules. Spectrophotometry was used to detect the presence of doxorubicin in the DNA derived from human neuroblastoma cell lines UKF-NB-4 and UKF-NB-4DOXO , exposed to this substance. This method, however, failed to detect the presence of doxorubicin. Keywords: neuroblastoma, doxorubicin, intrecalation, spectrophotometry
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