Mechanisms of sensitization by 8-chloro-adenosine of human tumor cells to TRAIL-induced apoptosis / 中华肿瘤杂志
Chinese Journal of Oncology
; (12): 586-590, 2005.
Article
em Zh
| WPRIM
| ID: wpr-358563
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To study the effect of 8-chloro-adenosine (8-Cl-Ado) on the sensitivity of human hepatoma and breast cancer cell lines to TRAIL-induced apoptosis in vitro and its mechanisms.</p><p><b>METHODS</b>Recombinant soluble TRAIL (rsTRAIL) or 8-Cl-Ado was used to treat hepatoma cell line BEL-7402 and breast cancer cell line MCF-7 in vitro. MTT assay was used to evaluate cell viability. The effect of cotreatment with rsTRAIL and 8-Cl-Ado was analyzed. NF-kappaB activity reporter plasmid was designed to measure the activity of transcription factor NF-kappaB. After transient transfection with the reporter plasmid, which contains NF-kappaB-responsive elements, into the cell lines, cells were treated with rsTRAIL and/or 8-Cl-Ado, then the activity of the reporter gene luciferase was determined. Different kinds of caspase inhibitors were used to measure the effect of caspases in the rsTRAIL and/or 8-Cl-Ado induced apoptosis.</p><p><b>RESULTS</b>8-Cl-Ado could greatly enhance sensitivity of BEL-7402 and MCF-7 cells to reTRAIL. Treatment with 8-Cl-Ado and rsTRAIL inactivated transcription factor NF-kappaB and induced apoptosis in BEL-7402, but not in MCF-7. Caspase family inhibitor could not prevent apoptosis induced by 8-Cl-Ado and rsTRAIL in BEL-7402 cells, however, it could block apoptosis in MCF-7 cells, indicating that two different apoptosis pathways in MCF-7 and BEL-7402 might exist, one was caspase dependent and the other caspase independent. Moreover, all of the inhibitors of caspse-3, -8 and -9 could not block apoptosis induced by the co-treatment.</p><p><b>CONCLUSION</b>8-chloro-adenosine can enhance the sensitivity of human hepatoma cell line BEL-7402 and breast cancer cell line MCF-7 to rsTRAIL, even though MCF-7 is TRAIL-resistant. 8-Cl-Ado combined with rsTRAIL can trigger different signal pathways in MCF-7 and BEL-7402, which are caspase dependent and independent, respectively.</p>
Texto completo:
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Base de dados:
WPRIM
Assunto principal:
Patologia
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Farmacologia
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Neoplasias da Mama
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Glicoproteínas de Membrana
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Transfecção
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2-Cloroadenosina
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NF-kappa B
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Fator de Necrose Tumoral alfa
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Apoptose
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Carcinoma Hepatocelular
Limite:
Humans
Idioma:
Zh
Revista:
Chinese Journal of Oncology
Ano de publicação:
2005
Tipo de documento:
Article