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L1210/VCR-1 and L1210/VCR-2 cell lines are multidrug resistant (MDR) sublines obtained by adaptation of mouse leukemic cell line L1210 to vincristine and, the development of MDR in these cell lines has been found to be associated with an overexpression of P-glycoprotein (PGP). In the present work we studied the relationship between the structure of 15(More)
Effect of specific inhibitors of extracellular-signal regulated protein kinase (ERK) pathway, PD98059 and U0126, on P-glycoprotein (Pgp)-mediated vincristine resistance of L1210/VCR cells was investigated. Both test inhibitors significantly reduced the survival of L1210/VCR cells in the presence of vincristine and this was associated with a decrease of LC50(More)
Effect of pentoxifylline (PTX) on vincristine (VCR) resistance of multidrug resistant L1210/VCR mouse leukemic cell line was studied. Reversal effect of PTX (in concentration 50-150 mg/l) on vincristine resistance, i.e. potentiation of vincristine cytotoxicity on L1210/VCR cells by PTX was found. PTX alone in the above concentration did not exert any(More)
Overexpression of P-glycoprotein (P-GP) accompanied by multidrug resistance (MDR) to diverse groups of cytostatics was developed by long-term adaptation of mouse leukemic cell line L1210 to vincristine. Two resistant sublines of cells characterized by ID50 values for vincristine 1.05 mg/l (L1210/VCR-1) and 2.3 mg/l (L1210/VCR-2), respectively, were used.(More)
Multidrug resistance (MDR) of cancer tissue is a phenomenon in which cancer cells exhibit reduced sensitivity to a large group of unrelated drugs with different mechanisms of pharmacological activity. Mechanisms that reduce cell sensitivity to damage induced by a variety of chemicals were found to be caused by diverse, albeit well-defined, phenotypic(More)
Eukaryotic cells respond to different external stimuli by activation of mechanisms of cell signaling. One of the major systems participating in the transduction of signal from the cell membrane to nuclear and other intracellular targets is the highly conserved mitogen-activated protein kinase (MAPK) superfamily. The members of MAPK family are involved in(More)
We report that SB203580 (SB), a specific inhibitor of p38-MAPK, protects pig myocardium against ischemic injury in an in vivo model. SB was applied by local infusion into the subsequently ischemic myocardium for 60 min before a 60-min period of coronary occlusion followed by 60-min reperfusion (index ischemia). Infarct size was reduced from a control value(More)
Omega-3 fatty acids (omega-3 FA) and statins exhibit besides lipid-lowering effects the antiarrhythmic ability in clinic, while definite mechanisms are not yet elucidated. Our goal was to examine whether these compounds can modulate inducibility of hypertriglyceridemic (HTG) rat heart to ventricular fibrillation (VF) and myocardial cell-to-cell coupling(More)
A vincristine resistant cell line was obtained from mouse leukemia cells L1210 by long-term adaptation in a medium with stepwise increasing concentrations of vincristine. By Western blotting using monoclonal antibody C219, positive signal on the presence of P-glycoprotein was observed in the resistant cells. Moreover, hybridization of mRNA from vincristine(More)
Multidrug resistance of murine leukaemic cell line L1210/VCR (obtained by adaptation of parental drug-sensitive L1210 cells to vincristine) is associated with overexpression of mdr1 gene product P-glycoprotein (Pgp)-the ATP-dependent drug efflux pump. 31P-NMR spectra of L1210 and L1210/VCR cells (the latter in the presence of vincristine) revealed, besides(More)