Design of antisense oligodeoxynucleotide targeting at bcl-2 mRNA and observation on its effect on the sensitivity of leukemia cells to arabinosyl cytosine / 中国实验血液学杂志
Journal of Experimental Hematology
;
(6): 41-44, 2003.
Artigo
em Chinês
| WPRIM
| ID: wpr-355719
ABSTRACT
The effective target sites for antisense oligodeoxynucleotides (AS-ODN) on bcl-2 mRNA, except its start region, were looked for and their effects on the sensitivity of HL-60 and K562 leukemia cells to arabinosyl cytosine (Ara-C) were observed. The secondary structure of bcl-2 mRNA was simulated with RNAstructure microsoftware, and AS-ODNs, targeting at some sites, were designed and synthesizd with phosphorothioate modifying. The median inhibitory concentration (IC(50)) of Ara-C for HL-60 and K562 cells was determined with MTT method; the apoptosis rate and bcl-2 protein expression level were assayed by flow cytometry. The results showed that 10 micro mol/L bcl-2 AS-ODN combined with Ara-C inhibited the expression of bcl-2 protein, increased apoptosis in HL-60 and K562 cells and decresed IC(50) of Ara-C significantly. The AS-ODN targeting the coding region of bcl-2 mRNA had stronger effect than AS-ODN targeting the translation initiation region. In conclusion, the much more effective sites for antisense oligodeoxynucleotides to target, except translation start region, might provide a new useful way for antisense drug design.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Patologia
/
Farmacologia
/
RNA Mensageiro
/
Dados de Sequência Molecular
/
Sequência de Bases
/
Desenho de Fármacos
/
Leucemia
/
Divisão Celular
/
Sobrevivência Celular
/
Química
Tipo de estudo:
Estudo diagnóstico
Limite:
Humanos
Idioma:
Chinês
Revista:
Journal of Experimental Hematology
Ano de publicação:
2003
Tipo de documento:
Artigo
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