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Synergistic antitumor effect of TRAIL and adriamycin on the human breast cancer cell line MCF-7
Cui, D. D; Huang, Y; Mao, S. H; Chen, S. C; Qiu, M; Ji, L. L; Yi, C.
Afiliação
  • Cui, D. D; Sichuan University. West China Hospital. Division of Abdominal Cancer. Chengdu. CN
  • Huang, Y; Sichuan University. West China School of Preclinical and Forensic Medicine. Department of Pathophysiology. Chengdu. CN
  • Mao, S. H; Sichuan University. West China School of Preclinical and Forensic Medicine. Department of Pathophysiology. Chengdu. CN
  • Chen, S. C; Chengdu Diao Pharmaceutical Group. Institute of Materia Medica. Chengdu. CN
  • Qiu, M; Sichuan University. West China Hospital. Division of Abdominal Cancer. Chengdu. CN
  • Ji, L. L; Sichuan University. West China School of Preclinical and Forensic Medicine. Department of Pathophysiology. Chengdu. CN
  • Yi, C; Sichuan University. West China Hospital. Division of Abdominal Cancer. Chengdu. CN
Braz. j. med. biol. res ; 42(9): 854-862, Sept. 2009. ilus, graf
Article em En | LILACS | ID: lil-524323
Biblioteca responsável: BR1.1
ABSTRACT
The aim of the present study was to determine the effect of the combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and adriamycin (ADM) on the human breast cancer cell line MCF-7 and to identify potential mechanisms of apoptosis. Cell viability was analyzed by the MTT assay and the synergistic effect was assessed by the Webb coefficient. Apoptosis was quantified using the annexin V-FITC and propidium iodide staining flow cytometry. The mRNA expression of TRAIL receptors was measured by RT-PCR. Changes in the quantities of Bax and caspase-9 proteins were determined by Western blot. MCF-7 cells were relatively resistant to TRAIL (IC50 >10 µg/mL), while MCF-7 cells were sensitive to ADM (IC50 <10 µg/mL). A subtoxic concentration of ADM (0.5 µg/mL) combined with 0.1, 1, or 10 µg/mL TRAIL had a synergistic cytotoxic effect on MCF-7 cells, which was more marked with the combination of TRAIL (0.1 µg/mL) and ADM (0.5 µg/mL). In addition, the combined treatment with TRAIL and ADM significantly increased cell apoptosis from 9.8 percent (TRAIL) or 17 percent (ADM) to 38.7 percent, resulting in a synergistic apoptotic effect, which is proposed to be mediated by up-regulation of DR4 and DR5 mRNA expression and increased expression of Bax and caspase-9 proteins. These results suggest that the combination of TRAIL and ADM might be a promising therapy for breast cancer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: LILACS Assunto principal: Neoplasias da Mama / Doxorrubicina / Apoptose / Ligante Indutor de Apoptose Relacionado a TNF / Antibióticos Antineoplásicos Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Braz. j. med. biol. res Assunto da revista: BIOLOGIA / MEDICINA Ano de publicação: 2009 Tipo de documento: Article / Project document País de afiliação: China País de publicação: Brasil
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: LILACS Assunto principal: Neoplasias da Mama / Doxorrubicina / Apoptose / Ligante Indutor de Apoptose Relacionado a TNF / Antibióticos Antineoplásicos Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Braz. j. med. biol. res Assunto da revista: BIOLOGIA / MEDICINA Ano de publicação: 2009 Tipo de documento: Article / Project document País de afiliação: China País de publicação: Brasil