Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
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Query: UMLS:C0026764 (
multiple myeloma
)
36,148
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
XAF1
is a newly identified candidate tumour-suppressor gene that can antagonise XIAP and sensitise cells to cell death triggers. This study was undertaken to study the effect of 5-azacytidine (AZA) on
XAF1
expression in
myeloma
cells and efficacy of 5-AZA and arsenic trioxide (ATO) combination treatment in
myeloma
in vivo and in vitro.
XAF1
expression was analysed by semi-quantitative PCR and western blotting. Methylation specific PCR was used to detect methylation status of
XAF1
promoter CpG islands. RPMI 8226 and XG-7 cells were treated with various concentrations of 5-AZA and ATO. Expression of
XAF1
mRNA variants were confirmed by gel electrophoresis and sequencing. Untreated RPMI 8226 cell expresses two variants of
XAF1
mRNA. Untreated XG-7 cell has no expression of
XAF1
. Hypermethylation of
XAF1
promoter CpG islands was detected in both cell lines. Both cell lines express full-length
XAF1
transcript after treated with 2.5 mumol/L 5-AZA for 72 h. Our studies demonstrated that 5-AZA exhibits anti-
myeloma
synergy with ATO. In addition, ATO alone, 5-AZA alone, or combination of 5-AZA and ATO was effective in slowing
myeloma
growth and prolonging survival of
myeloma
-loaded nude mice. The findings suggested that 5-AZA and ATO may be an effective combination in the therapy of
myeloma
patients.
...
PMID:Combination of DNA methylation inhibitor 5-azacytidine and arsenic trioxide has synergistic activity in myeloma. 1907 51
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
.
...
PMID:Preliminary study on 5-azacytidine anti-myeloma activity in vitro. 1954 72
