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Tumour Biol ; 35(8): 8023-31, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24839008

RESUMO

RLIP76 is known to play a role in cell growth, division, apoptosis, and chemosensitivity in various malignant cancer cells. However, few studies have been done on the role of RLIP76 in leukemia. In this study, human leukemia cell line U937 was transiently transfected with a RLIP76-targeted short hairpin RNA (shRNA) to investigate the effects of RLIP76 on cellular functions. Real-time PCR and western blot analysis revealed that the expression levels of RLIP76 mRNA and protein in U937 cells were significantly suppressed after transfection with shRNA-containing vector. Knockdown of RLIP76 significantly inhibited cell growth and decreased the colony formation rate, as assessed by trypan blue exclusion and colony formation assay. Flow cytometry analysis showed that reduced RLIP76 expression resulted in cell cycle arrest at G1 phase and induced apoptosis. Meanwhile, western blot analysis demonstrated that RLIP76 knockdown increased expression of Bax, cleaved caspase-3/-9, and cleaved poly (ADP-ribose) polymerase (PARP) but reduced the expression of cyclin D1, cyclin E, and Bcl-2 in U937 cells. Finally, knockdown of RLIP76 in U937 cells also enhanced their chemosensitivity to daunorubicin. Taken together, this study suggests that RLIP76 is a potential target for developing novel therapeutic strategies for leukemia.


Assuntos
Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Antibióticos Antineoplásicos/farmacologia , Apoptose , Daunorrubicina/farmacologia , Proteínas Ativadoras de GTPase/antagonistas & inibidores , Leucemia/tratamento farmacológico , Interferência de RNA , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/fisiologia , Pontos de Checagem do Ciclo Celular , Diferenciação Celular , Proliferação de Células , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/fisiologia , Humanos , Leucemia/patologia , RNA Interferente Pequeno/genética , Células U937
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