PSC 833 modulation of multidrug resistance to paclitaxel in cultured human ovarian carcinoma cells leads to apoptosis.
Anticancer Res
; 22(6A): 3425-8, 2002.
Article
em En
| MEDLINE
| ID: mdl-12530099
ABSTRACT
BACKGROUND:
Multidrug resistance (MDR) modulator PSC 833 has been shown to modulate multidrug resistance in Pg-p-positive human ovarian carcinoma cells A2780/ADR. Co-treatment of A2780/ADR cells with paclitaxel (PTX) and PSC 833 resulted in the restoration of PTX-sensitivity comparable to that in parental A2780 cells.RESULTS:
The flow cytometry experiments presented here showed PTX-(A2780) and PTX plus PSC 833 (A2780/ADR)-induced cell accumulation in the G2/M-phase of the cell cycle with concomitant appearance of apoptotic cells with sub-G0 (hypodiploid) DNA content. Furthermore, these events were accompanied by the appearance of poly(ADP-ribose) polymerase (PARP) cleavage, up-regulation of Bax, p53 and p21WAF1/CIP1 proteins and internucleosomal DNA fragmentation. Interestingly, we did not detect any significant alterations in Bcl-xL, CD95/Fas and Fas-L protein levels.CONCLUSION:
These results demonstrate the PSC 833 reduced the Pg-p-mediated multidrug resistance in human ovarian carcinoma cells to PTX-induced apoptosis in vitro.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Paclitaxel
/
Resistência a Múltiplos Medicamentos
/
Proteínas Proto-Oncogênicas c-bcl-2
/
Ciclosporinas
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article