Histone Deacetylase Inhibitor Saha Suppressed The Proliferation Of Multiple Myeloma Cell In Vitro And In Vivo

Objective:To determine the anti-myeloma effect of SAHA(suberoylanilide hydroxamic acid)and its mechanism in mouse myeloma cell line SP2/0 in vitro and in vivoMaterials and methods:The inhibitory effects of SAHA on SP2/0 cells were measured by CCK-8assay,and the apoptosis and cell cycle was analyzed by FACS.The protein of Caspase-3 and p53 of SP2/0 cells treated with SAHA were examined by Western-blot analysis.Annexin V/7-AAD double staining was performed to detect the apoptosis of SP2/0 induced by SAHA in vitro.SP2/0 cells(1×10~6)resuspended in200μL PBS were inoculated subcutaneously and intravenously into BALB/c mice which established aggressive or non-aggressive myeloma-bearing mouse models respectively.On day 3 after inoculation,mice were receiving SAHA or vehicle control treatment by intraperitoneal injection.The dose of SAHA was 60 mg/(kg·d),5 days a week for 3 weeks.Results:In SAHA-treated SP2/0 cells,the proliferation inhibition rate and apoptotic cells increased in a dose dependent manner.Also,SAHA significantly increased the proportion of cells in G2 phase and decreased the proportion of cells in S phase.Molecular mechanisms of apoptosis and cell cycle arrest of SP2/0 induced by SAHA were in part correlated with up-regulating the expression level of Caspase-3 and p53.In the non-aggressive myeloma-bearing mice,SP2/0 cells disappeared in peripheral blood after SAHA treatment.In the aggressive myeloma-bearing mice,inhibited tumor growth and prolonged the survival were observed after SAHA treatment.Conclusion:SAHA inhibited SP2/0 cells proliferation associated with inducing apoptosis and cell cycle arrest,the mechanisms of action,at least in part,by the activating Caspase-3 and p53 pathway.