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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1987-3-16
pubmed:abstractText
Reserpine enhanced in vitro the cytotoxicity of 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) in both the C6 glioma and its ACNU-resistant subline, C6/ACNU. Reserpine also enhanced the chemotherapeutic effect of ACNU in C6/ACNU-bearing (C6/ACNU-meningeal gliomatosis) rats, in which ACNU resistance could be modulated by combined ACNU and reserpine therapy. When 10 microM reserpine was added to ACNU in culture, the concentration of drug required for 50% inhibition of cell growth (IC50) of ACNU for C6/ACNU cells decreased to the level of that for C6 cells. When 20 microM reserpine was added to the culture, intracellular uptake of ACNU in C6/ACNU cells increased further and the efflux of the drug from the cells decreased. In in vivo experiments in rats, combined chemotherapy with ACNU (1 mg/kg) and reserpine (250 micrograms/kg) by intrathecal injection significantly increased the life span of the rats as compared to results with ACNU chemotherapy alone. The enhanced cytotoxicity of ACNU in ACNU-resistant glioma cells in vitro and in vivo may be explained by the increase of intracellular concentration of ACNU resulting from the inhibition of ACNU efflux from the resistant cells by reserpine. It was concluded that ACNU resistance could be modulated in vitro and in vivo by combined therapy with ACNU and reserpine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-3085
pubmed:author
pubmed:issnType
Print
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
251-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Modulation in vitro and in vivo of ACNU resistance in a subline of C6 glioma with reserpine.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't