Synergistic induction of apoptosis by the combination of TRAIL and chemotherapy in chemoresistant ovarian cancer cells

Simple item page
dc.contributor.authorCuello, M
dc.contributor.authorEttenberg, SA
dc.contributor.authorNau, MM
dc.contributor.authorLipkowitz, S
dc.date.accessioned2025-01-21T01:30:49Z
dc.date.available2025-01-21T01:30:49Z
dc.date.issued2001
dc.description.abstractObjectives. The aim of this study was to investigate whether TNF-related apoptosis-inducing ligand (TRAIL) alone or in combination with chemotherapy could induce apoptosis in ovarian cancer cells resistant to chemotherapy,
dc.description.abstractMethods. Twelve chemoresistant epithelial cancer cell lines were treated with each chemotherapeutic drug alone (cisplatin, doxorubicin, or paclitaxel), TRAIL alone, or the combination. Toxicity was assessed using the MTS assay. To assess whether growth inhibition was due to apoptosis, TUNEL assay, caspase activation (measured by caspase-3 and PARP cleavage), and the sub G0/G1 fraction of cells were measured. Synergism was confirmed by fractional inhibition and dose- effect analysis. Expression of death and decoy receptors was studied by immunoblotting and an RNase protection assay. Statistical comparison of means was performed using Student's t test.
dc.description.abstractResults. The majority of the chemoresistant cells were also resistant to TRAIL alone. In contrast, the combination of TRAIL and chemotherapy resulted in a significant growth inhibition over a wide range of concentrations. This interaction was synergistic by dose-effect analysis. Flow cytometry demonstrated a significant increase in the fraction of apoptotic cells by the combination compared to each reagent alone. A significant enhancement in caspase and PARR cleavage was observed upon treatment with the combination. Finally, no correlation between induction of apoptosis and level of death receptors was found.
dc.description.abstractConclusions. The data suggest that almost all the ovarian cancer cells, which are resistant to chemotherapy, are also resistant to TRAIL, The combination of TRAIL and chemotherapy overcomes this resistance in a synergistic fashion by triggering caspase-mediated apoptosis. The combination of TRAIL and chemotherapy could be useful as a therapy for chemoresistant ovarian cancers. (C) 2001 Academic Press.
dc.fuente.origenWOS
dc.identifier.doi10.1006/gyno.2001.6194
dc.identifier.eissn1095-6859
dc.identifier.issn0090-8258
dc.identifier.urihttps://doi.org/10.1006/gyno.2001.6194
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96900
dc.identifier.wosidWOS:000169233500007
dc.issue.numero3
dc.language.isoen
dc.pagina.final390
dc.pagina.inicio380
dc.revistaGynecologic oncology
dc.rightsacceso restringido
dc.subjectTRAIL
dc.subjectapoptosis
dc.subjectovarian cell line
dc.subjectchemotherapy
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleSynergistic induction of apoptosis by the combination of TRAIL and chemotherapy in chemoresistant ovarian cancer cells
dc.typeartículo
dc.volumen81
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
Files
Collections
Artículos de revistas