Growth and gene expression of leukemia cell after treated with methylation inhibitor 5-aza-2'-deoxycytidine / 中华血液学杂志
Chinese Journal of Hematology
;
(12): 486-490, 2004.
Artigo
em Chinês
| WPRIM
| ID: wpr-291391
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the mechanism of demethylation therapy of leukemia by 5-aza-2'-deoxycytidine (5-aza-CdR).</p><p><b>METHODS</b>By using MTT test, NBT reduction reaction and DNA agarose gel electrophoresis, changes in proliferation, differentiation and apoptosis were observed in K562, HL-60 and fresh leukemia cells after treated with 5-aza-CdR. The mRNA expressions of DNMTs, p15, p53 and bcl-2 were measured by RT-PCR. The status of p15(INK4B) gene methylation was examined by methylation-specific PCR (MSP-PCR).</p><p><b>RESULTS</b>The growth inhibition of K562, HL-60 and fresh leukemia cells displayed a dose and time-dependent manner after treated by 5-aza-CdR. The differentiation-inducing ability on HL-60 cells was obvious at 0.5 micromol/L of 5-aza-CdR. The up-regulation of p15 mRNA and p53 mRNA expression and down-regulation of bcl-2 mRNA expression were obvious as compared with the control, but the DNMTs expression was not significantly different from the control. The methylation status of p15 gene in fresh leukemia cells decreased gradually with increasing concentration of 5-aza-CdR.</p><p><b>CONCLUSION</b>The proliferation of leukemia cells was obviously inhibited by 5-aza-CdR, its mechanism maybe related to the up-regulation of p15 and p53 genes and down-regulation of bcl-2 gene. The decrease of p15 gene methylation was associated with the competitive inhibition of 5-aza-CdR.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Azacitidina
/
RNA Mensageiro
/
Metilases de Modificação do DNA
/
Regulação Neoplásica da Expressão Gênica
/
Transformação Celular Neoplásica
/
Apoptose
/
Proteínas de Ciclo Celular
/
Células HL-60
/
Metilação de DNA
Limite:
Humanos
Idioma:
Chinês
Revista:
Chinese Journal of Hematology
Ano de publicação:
2004
Tipo de documento:
Artigo
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