Resistance to paclitaxel mediated by P-glycoprotein can be modulated by changes in the schedule of administration.
Cancer Chemother Pharmacol
; 40(3): 245-50, 1997.
Article
em En
| MEDLINE
| ID: mdl-9219509
ABSTRACT
PURPOSE:
Increasing use of paclitaxel in clinical oncology has stimulated interest in its mechanisms of resistance and ways to overcome these. Studies were performed with paclitaxel to determine the role of P-glycoprotein in drug sensitivity, and the effect of schedule on relative resistance. We have previously reported that prolonged exposure to P-glycoprotein substrates decreases relative resistance in multidrug resistant cells.METHODS:
Using both unselected and drug-selected cell lines, cross-resistance and cytotoxicity reversal studies using cyclosporin A were performed. In multidrug-resistant cells, cross-resistance was evaluated after 3-, 24-, and 96-h exposures to paclitaxel.RESULTS:
Cross-resistance to paclitaxel in P-glycoprotein-expressing sublines was shown to be comparable to that of other drugs transported by P-glycoprotein. Sensitivity to paclitaxel could be modulated by cyclosporin A in unselected cell lines expressing P-glycoprotein and not in P-glycoprotein-negative cell lines. Resistance to paclitaxel was reduced tenfold by increasing the duration of exposure in P-glycoprotein-expressing cells. This effect was not observed in a paclitaxel-resistant cell line which does not express P-glycoprotein.CONCLUSIONS:
These studies extend observations on the schedule dependence of paclitaxel cytotoxicity and the role of P-glycoprotein in mediating paclitaxel sensitivity. The schedule dependence of relative resistance suggests that infusional paclitaxel may help in overcoming P-glycoprotein-mediated resistance.
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Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Células Tumorais Cultivadas
/
Paclitaxel
/
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
/
Resistência a Múltiplos Medicamentos
/
Resistencia a Medicamentos Antineoplásicos
/
Antineoplásicos Fitogênicos
Limite:
Female
/
Humans
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
1997
Tipo de documento:
Article