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@article{1298332,
author = {Neradil, Jakub and Pavlasová, Gabriela and Šrámek, Martin and Kýr, Michal and Veselská, Renata and Štěrba, Jaroslav},
article_location = {Athens},
article_number = {5},
doi = {http://dx.doi.org/10.3892/or.2015.3819},
keywords = {methotrexate; leucovorin; osteosarcoma; resistance; antifolate; medulloblastoma},
language = {eng},
issn = {1021-335X},
journal = {Oncology Reports},
title = {DHFR-mediated effects of methotrexate in medulloblastoma and osteosarcoma cells: The same outcome of treatment with different doses in sensitive cell lines},
url = {http://www.spandidos-publications.com/or/33/5/2169},
volume = {33},
year = {2015}
}
TY - JOUR
ID - 1298332
AU - Neradil, Jakub - Pavlasová, Gabriela - Šrámek, Martin - Kýr, Michal - Veselská, Renata - Štěrba, Jaroslav
PY - 2015
TI - DHFR-mediated effects of methotrexate in medulloblastoma and osteosarcoma cells: The same outcome of treatment with different doses in sensitive cell lines
JF - Oncology Reports
VL - 33
IS - 5
SP - 2169-2175
EP - 2169-2175
PB - Spandidos Publications Ltd
SN - 1021335X
KW - methotrexate
KW - leucovorin
KW - osteosarcoma
KW - resistance
KW - antifolate
KW - medulloblastoma
UR - http://www.spandidos-publications.com/or/33/5/2169
L2 - http://www.spandidos-publications.com/or/33/5/2169
N2 - Although methotrexate (MTX) is the most well-known antifolate included in many standard therapeutic regimens, substantial toxicity limits its wider use, particularly in pediatric oncology. Our study focused on a detailed analysis of MTX effects in cell lines derived from two types of pediatric solid tumors: medulloblastoma and osteosarcoma. The main aim of this study was to analyze the effects of treatment with MTX at concentrations comparable to MTX plasma levels in patients treated with high-dose or low-dose MTX. The results showed that treatment with MTX significantly decreased proliferation activity, inhibited the cell cycle at S-phase and induced apoptosis in Daoy and Saos-2 reference cell lines, which were found to be MTX-sensitive. Furthermore, no difference in these effects was observed following treatment with various doses of MTX ranging from 1 to 40 µM. These findings suggest the possibility of achieving the same outcome with the application of low-dose MTX, an extremely important result, particularly for clinical practice. Another important aspect of treatment with high-dose MTX in clinical practice is the administration of leucovorin (LV) as an antidote to reduce MTX toxicity in normal cells. For this reason, the combined application of MTX and LV was also included in our experiments; however, this application of MTX together with LV did not elicit any detectable effect. The expression analysis of genes involved in the mechanisms of resistance to MTX was a final component of our study, and the results helped us to elucidate the mechanisms of the various responses to MTX among the cell lines included in our study.
ER -
NERADIL, Jakub, Gabriela PAVLASOVÁ, Martin ŠRÁMEK, Michal KÝR, Renata VESELSKÁ and Jaroslav ŠTĚRBA. DHFR-mediated effects of methotrexate in medulloblastoma and osteosarcoma cells: The same outcome of treatment with different doses in sensitive cell lines. \textit{Oncology Reports}. Athens: Spandidos Publications Ltd, 2015, vol.~33, No~5, p.~2169-2175. ISSN~1021-335X. Available from: https://dx.doi.org/10.3892/or.2015.3819.
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