A combination of STI571 and BCR-ABL1 siRNA with overexpressed p15INK4B induced enhanced proliferation inhibition and apoptosis in chronic myeloid leukemia
Braz. j. med. biol. res
;
47(12): 1096-1101, 12/2014. graf
Artigo
em Inglês
| LILACS
| ID: lil-727664
ABSTRACT
p15INK4B, a cyclin-dependent kinase inhibitor, has been recognized as a tumor suppressor. Loss of or methylation of the p15INK4B gene in chronic myeloid leukemia (CML) cells enhances myeloid progenitor formation from common myeloid progenitors. Therefore, we examined the effects of overexpressed p15INK4B on proliferation and apoptosis of CML cells. Overexpression of p15INK4B inhibited the growth of K562 cells by downregulation of cyclin-dependent kinase 4 (CDK4) and cyclin D1 expression. Overexpression of p15INK4B also induced apoptosis of K562 cells by upregulating Bax expression and downregulating Bcl-2 expression. Overexpression of p15INK4B together with STI571 (imatinib) or BCR-ABL1 small interfering RNA (siRNA) also enhanced growth inhibition and apoptosis induction of K562 cells. The enhanced effect was also mediated by reduction of cyclin D1 and CDK4 and regulation of Bax and Bcl-2. In conclusion, our study may provide new insights into the role of p15INK4B in CML and a potential therapeutic target for overcoming tyrosine kinase inhibitor resistance in CML.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Piperazinas
/
Pirimidinas
/
Benzamidas
/
Leucemia Mielogênica Crônica BCR-ABL Positiva
/
Proteínas de Fusão bcr-abl
/
Apoptose
/
RNA Interferente Pequeno
/
Proliferação de Células
Limite:
Humanos
Idioma:
Inglês
Revista:
Braz. j. med. biol. res
Assunto da revista:
Biologia
/
Medicina
Ano de publicação:
2014
Tipo de documento:
Artigo
País de afiliação:
China
Instituição/País de afiliação:
Fourth Military Medical University/CN
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