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Apoptosis ; 12(1): 73-85, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17136491

RESUMO

Cancer of the reproductive tract encompasses malignancies of the uterine corpus, cervix, ovary, Fallopian tube, among others and accounts for 15% of female cancer mortalities. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) mediates apoptosis by binding to death receptors and offers a promising cancer treatment. The goal of this study was to investigate and characterize the effect of TRAIL in endometrial cancer cell lines and normal (non-cancerous) epithelial cells of endometrial origin. We also examined the effect of TRAIL in other primary cultured cancers and normal cells of the human female reproductive tract and evaluated if TRAIL mediated apoptosis correlated with death receptors and decoy receptors 1 and 2.Herein, we demonstrate that TRAIL at concentrations which kill cancerous cells, does not mediate apoptosis or alter cell viability in normal human endometrium, ovary, cervix or Fallopian tube. The partial inhibition by a caspase 9 inhibitor and the total inhibition by a caspase 8 inhibitor demonstrates the dependency on the extrinsic apoptotic pathway. The selective mortality does not correlate with the presence of death or decoy receptors. These results suggest that TRAIL may be an effective treatment for endometrial cancer and other female reproductive cancers, with minimal secondary effects on healthy tissue.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/patologia , Genitália Feminina/efeitos dos fármacos , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Apoptose/genética , Apoptose/fisiologia , Sequência de Bases , Linhagem Celular Tumoral , Células Cultivadas , DNA Complementar/genética , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/fisiopatologia , Endométrio/citologia , Endométrio/efeitos dos fármacos , Endométrio/fisiologia , Feminino , Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/fisiopatologia , Genitália Feminina/citologia , Genitália Feminina/fisiologia , Humanos , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/fisiologia , Proteínas Recombinantes/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/fisiologia , Células Tumorais Cultivadas
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