Abstract:

Objective To explore the possible relationship between alteration of cell cycle and JAK/STAT3 signal transduction pathway inhibition induced by arsenic trioxide (As₂O₃) in myeloma cell lines U266 and RPMI8226 in vitro. Methods Multiple myeloma cell lines U266 and RPMI8226 were used as in vitro models. The influence of As₂O₃ on myeloma cells were evaluated by MTT assay and flow cytometry. Meanwhile, methylation specific PCR and Western blotting were employed to detect the methylation status of gene SOCS-1 and protein expression level of P-STAT3 in these cells after As₂O₃ treatment. Results As₂O₃ significantly inhibited the growth of U266 and RPMI8226 cells in a dose-dependent manner. Furthermore, cell cycle was arrested at G₀/G₁ phase with inhibition of protein expression level of P-STAT3 and SOCS-1 gene demethylation after exposure to As₂O₃ for 72 h（r=0.85, P<0.05）. Conclusion As₂O₃ could induce the alteration of cell cycle which might be related to JAK/STAT3 signal transduction pathway inhibition and SOCS-1 demethylation in myeloma cell lines. The study puts forward a new idea of As₂O₃ treatment in multiple myeloma.

Key words: arsenic trioxide, myeloma, SOCS-1, JAK/STAT3, cell cycle