二硫化二砷对MDS骨髓单个核细胞凋亡、组蛋白乙酰化和TLR2活化的影响

Abstract

Objective As the main component of traditional Chinese medicine realgar, arsenic disulfide (As 2 S 2 ) is widely used in treating myelodysplastic syndromes (MDS). The goal of the current study is to assess the effects of As 2 S 2 on bone marrow mononuclear cells (BMMNC) of MDS. Methods BMMNCs were obtained from 10 lower risk MDS patients, 5 higher risk MDS patients, and 3 healthy controls. Then, the cells were treated with As 2 S 2 for 48   h, using vorinostat (also known as SAHA) as control. Cell proliferation and apoptosis were detected. mRNA and protein levels of histone deacetylase-1 (HDAC1), Toll-like receptor 2 (TLR2), and erythroid transcription factor (GATA-1) were detected by quantitative real-time PCR and western blot analysis. Results After As 2 S 2 treatment in concentrations ranging from 3.125 to 100   μmol/L, cell proliferation was inhibited in both lower risk and higher risk MDS. Fifty percent inhibitory concentrations were 24.4   μmol/L and 23.6   μmol/L, respectively, for lower and higher risk MDS. Apoptotic cells significantly increased in both types of MDS. mRNA and protein levels of HDAC1 and TLR2 were reduced, whereas GATA-1 was increased in both types of MDS. Conclusions As 2 S 2 could inhibit cell proliferation and induce apoptosis through histone acetylation modulation in MDS. Similar to SAHA, As 2 S 2 could reduce TLR2 activation and increase GATA-1 expression. Current data suggest epigenetic and immunological alternations are involved in therapeutic mechanisms of realgar in the treatment of MDS.