Abstract: Objective To investigate the effects of arsenic trioxide (AS₂O₃) on SOCS-1 gene methylation and expression of P-STAT3 in multiple myeloma (MM) cells. Methods MM cell lines U266 and CZ-1 were used as in vitro models. Methylation status of SOCS-1 gene was detected by the methylation specific PCR（MSP）while P-STAT3 protein expression was determined by Western blotting assay before and after AS2O3 treatment. Meanwhile growth inhibition and apoptosis of MM cells were determined by flow cytometry. Results Hypermethylation of SOCS-1 gene was observed in each MM cell line compared with wide type．After exposure to AS₂O₃, it was shown that SOCS1 gene was demethylated obviously, meanwhile the expression level of P-STAT3 protein and cell proliferation was inhibited significantly in each cell line. The apoptosis rate was increased. When U266 and CZ-1 were treated with AS₂O₃ of  0,0.5,1.0,2.0 μmol/L respectively, the total cell apoptosisis ratio of U266 was 0.06%,0.56%,48.96%,61.07%(χ²=9.19, P<0.05); and the total cell apoptosisis ratio of CZ-1 was 4.2%,,40.3%,,47.72%,,68.49%(χ²=8.96, P<0.05). Conclusion AS₂O₃could inhibit JAK/STAT signal transduction pathway by inducing SOCS-1 gene demethylation in MM cells which might be related to cell apoptosis.

Key words: Multiple myeloma, Methylation, Apoptosis, Arsenic trioxide, SOCS-1 gene