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Preliminary study on 5-azacytidine anti-myeloma activity in vitro / 中国实验血液学杂志
Article em En | WPRIM | ID: wpr-334061
Biblioteca responsável: WPRO
ABSTRACT
This study was aimed to investigate the effect of 5-azacytidine (5-AZA) on XAF1 expression in myeloma cells and efficacy of 5-AZA treatment for myeloma in vitro. XAF1 expression was analyzed by semi-quantitative PCR. Methylation-specific PCR (MSP) was used to detect the methylation status of XAF1 promoter CpG islands. RPMI 8226 and XG-7 cells were treated with 0-5 micromol/L of 5-AZA. Expression of XAF1 mRNA variants was confirmed by gel electrophoresis. The results indicated that the untreated RPMI 8226 cell expressed XAF1 mRNA transcript 1 and transcript 2, untreated XG-7 cells did not express XAF1 mRNA. Hypermethylation of XAF1 promoter CpG islands could be detected in both cell lines. Both cell lines expressed full-length XAF1 transcript after being treated with 2.5 micromol/L of 5-AZA for 72 hours. 5-AZA treatment led XAF1 promoter CpG island to hypomethylation in both cell lines. 5-AZA exerted anti-myeloma activity in a time- and concentration-dependent manner. The IC(50) value of XG-7 cells treated with 5-AZA for 48 hours was 2.6 micromol/L. 1.0, 2.0, 2.5 and 5.0 micromol/L of 5-AZA treatment for 48 hours induced (34.3 +/- 8.0)%, (54.8 +/- 3.1)%, (64.1 +/- 3.4)%, (81.0 +/- 4.1)% apoptosis in XG-7 cell line respectively. The combination of 1.0 - 4.0 micromol/L of 5-AZA with 1.0 - 4.0 micromol/L of arsenic trioxide (ATO) exhibited synergistic toxicity in myeloma cells with all CI values less than 1.0. It is concluded that lack of XAF1 expression and abnormal expression of XAF1 in myeloma cell lines are associated with the hypermethylation of XAF1 gene promoter CpG island. 5-AZA treatment can induce the expression of XAF1 mRNA and protein in myeloma. 5-AZA exerts anti-myeloma activity via apoptosis at clinically achievable concentrations. The findings suggested that 5-AZA and ATO may be an effective combination in the therapy of patients with multiple myeloma.
Assuntos
Texto completo: 1 Índice: WPRIM Assunto principal: Farmacologia / Azacitidina / Regiões Promotoras Genéticas / Apoptose / Linhagem Celular Tumoral / Peptídeos e Proteínas de Sinalização Intracelular / Proliferação de Células / Metabolismo / Mieloma Múltiplo / Proteínas de Neoplasias Limite: Humans Idioma: En Revista: Journal of Experimental Hematology Ano de publicação: 2009 Tipo de documento: Article
Texto completo: 1 Índice: WPRIM Assunto principal: Farmacologia / Azacitidina / Regiões Promotoras Genéticas / Apoptose / Linhagem Celular Tumoral / Peptídeos e Proteínas de Sinalização Intracelular / Proliferação de Células / Metabolismo / Mieloma Múltiplo / Proteínas de Neoplasias Limite: Humans Idioma: En Revista: Journal of Experimental Hematology Ano de publicação: 2009 Tipo de documento: Article