DHFR-mediated effects of methotrexate in medulloblastoma and osteosarcoma cells: the same outcome of treatment with different doses in sensitive cell lines

Oncology Reports
Jakub NeradilJaroslav Sterba

Abstract

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 c...Continue Reading

References

Nov 13, 2004·The Journal of Gene Medicine·Olaf J C HellwinkelHartmut Kabisch
Dec 15, 2005·Journal of Theoretical Biology·Yehuda G AssarafRon Y Pinter
Feb 27, 2007·Cancer Metastasis Reviews·Ying Huang
Mar 3, 2007·Cancer Metastasis Reviews·Yehuda G Assaraf
Feb 26, 2008·Leukemia & Lymphoma·Alan Kambiz Fotoohi, Freidoun Albertioni
Apr 22, 2010·Molecular Cancer Research : MCR·Jennifer J JordanMichael A Resnick
Oct 16, 2010·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Seong-Ae YoonJin-Hyoung Kang
Jun 29, 2011·British Journal of Clinical Pharmacology·Laila HolmboeKirsten Sundby Hall
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Sep 17, 2013·Pediatric Blood & Cancer·Ian Joseph Cohen, Johannes E Wolff
Oct 5, 2013·Gene·Fakhira Hassan NazkiBashir Ahmad Ganaie
Mar 22, 2014·Neurotoxicity Research·Tânia CapelôaAna P Silva

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Methods Mentioned

BETA
biopsy
PCR
electrophoresis
flow cytometry

Software Mentioned

BD FACSuite
ImageJ

Related Concepts

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