Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand cooperates with chemotherapy to inhibit orthotopic lung tumor growth and improve survival.
Cancer Res
; 64(14): 4900-5, 2004 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-15256461
ABSTRACT
Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is a tumor necrosis factor superfamily member that induces apoptosis through the death receptors DR4 and/or DR5 in various cancer cell types but not in most normal cells. Several lung cancer cell lines express DR4 and DR5 and undergo apoptosis in vitro in response to Apo2L/TRAIL. We investigated the efficacy of recombinant soluble human Apo2L/TRAIL and its interaction with chemotherapy in xenograft models based on human NCI-H460 non-small cell lung carcinoma cells. In vitro, Taxol enhanced caspase activation and apoptosis induction by Apo2L/TRAIL. In vivo, Apo2L/TRAIL or Taxol plus carboplatin chemotherapy partially delayed progression of established subcutaneous tumor xenografts, whereas combined treatment caused tumor regression and a substantially longer growth delay. Apo2L/TRAIL, chemotherapy, or the combination of both inhibited growth of preformed orthotopic lung parenchymal tumors versus control by 60%, 57%, or 97%, respectively (all P < 0.01; n = 8-10). Furthermore, combination treatment improved day-90 survival relative to control (7 of 15 versus 1 of 15; P = 0.0003 by Mantel-Cox) as well as to Apo2L/TRAIL (3 of 14; P = 0.031) or chemotherapy (3 of 15; P = 0.035). These studies provide evidence for in vivo activity of Apo2L/TRAIL against lung tumor xenografts and underscore the potential of this ligand for advancing current lung cancer treatment strategies.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Fator de Necrose Tumoral alfa
/
Carcinoma Pulmonar de Células não Pequenas
/
Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos