[Correlation of cell cycle alteration to SOCS-1 gene demethylation induced by arsenic trioxide in myeloma cell lines].

Background and Objective: Recent studies suggest that arsenic trioxide (AS 2 O 3 ) has strong therapeutic potential for multiple myeloma (MM), which may be due to AS 2 O 3 -induced demethylation of tumor suppressor genes. This study explored the correlation of cell cycle alteration to SOCS-1 gene demethylation after AS 2 O 3 induction in MM cell lines in vitro. Methods: MM cell lines U266 and RPMI8226 were used. Cell proliferation and cell cycle of MM cells after the treatment of AS 2 O 3 were assessed by MTT assay and flow cytometry, respectively. Methylation status was detected by methylation specific PCR (MSP-PCR), and gene expression of SOCS-1 was measured by real-time PCR in MM cells before and after AS 2 O 3 treatment. Results: AS 2 O 3 significantly inhibited the growth of U266 and RPMI8226 cells in a dose-dependent manner. The cell cycle of U266 and RPMI8226 were arrested at G 0 -G 1 phase. Compared with the wild type, the percentage of cells was increased at G 0 -G 1 phase, but decreased at S phase after the treatment of AS 2 O 3 for 72 h (p < 0.05). The mRNA expression of SOCS-1 gene was significantly increased with hemi-methylation (AS 2 O 3 , 0.5 μmol/L,72 h) or complete demethylation (AS 2 O 3 , 1.0 μmol/L or AS 2 O 3 , 2.0 μmol/L,72 h) of the SOCS-1 gene in comparison with the wild type (p < 0.05). Conclusions: AS 2 O 3 could induce cell cycle alteration of MM, which might be related to demethylation and re-expression of SOCS-1 gene in MM cell lines. The study might provide a new approach to elucidate the mechanism of the antitumor effect of AS 2 O 3 in MM. Multiple myeloma (MM) is one class of hematic malignant tumor characterized by a large number of plasma cells clonally expanded. Current opinion is that the pathogenesis and development of the disease is closely linked to suppressors of cytokine signaling-1 protein (SOCS-1). Recent domestic and international studies 1 have shown that a high dose of AS 2 O 3 can induce apoptosis and inhibit tumor by inducing cell cycle arrest, although its specific mechanisms are still not fully understood. We applied myeloma cell lines U266 and RPMI8226 as an in vitro experimental model to explore the possible correlation between AS 2 O 3 -induced cell cycle alteration of human myeloma cells and the intracellular demethylation of SOCS-1 gene.