[Inhibitory Effect of Histone Deacetylase Inhibitor SAHA on Proliferation of Mouse Multiple Myeloma Cell Line SP2/0 in vitro and in vivo].

OBJECTIVE: To explore the anti-myeloma effect of suberoylanilide hydroxamic acid (SAHA) and on mouse myeloma cell line SP2/0 in vitro and in vivo and its mechanism. METHODS: The inhibitory effect of SAHA on SP2/0 cells was measured by CCK-8 assay,and the apoptosis and cell cycle were analyzed by flow cytometry FACS. The protein expression of Caspase-3 and p53 of SP2/0 cells treated with SAHA were examined by Western blot. Annexin V/7-AAD double staining was performed to detect the apoptosis of SP2/0 induced by SAHA in vitro. SP2/0 cells (1×106) resuspended in 200 µl PBS were inoculated subcutaneously and intravenously into BALB/c mice, so as to establish aggressive or non-aggressive myeloma-bearing mouse models respectively. On day 3 after modeling, mice received SAHA or vehicle control treatment by intraperitoneal injection. The dose of SAHA was 60 mg/kg·d, 5 times 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 ratio of cells in G2 phase and decreased in S phase. Molecular mechanisms of apoptosis and cell cycle arrest of SP2/0 induced by SAHA partly 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, inhibition of tumor growth and prolongation of the cell survival were observed after SAHA treatment. CONCLUSION: SAHA inhibited SP2/0 cell proliferation, this effect associates with inducing apoptosis and cell cycle arrest, the mechanism of SAHA ralates partly with activating Caspase-3 and p53 pathway.

[Clinical features and therapeutic response of aplastic anemia patients with or without cytogenetic abnormalities].

OBJECTIVE: To compare clinical features and therapeutic response of patients with aplastic anemia with and without cytogenetic abnormalities. METHODS: Clinical features of 133 patients with successful chromosomal analysis were retrospectively studied, and therapeutic response between patients with and without cytogenetic abnormalities was compared. RESULTS: Cytogenetic abnormalities were found in 9 patients, which included trisomy 8 (4 cases), monosomy 7 (2 cases) and Xq- (1 case), 1q- (1 case) and 7q- (1 case). No significant difference was detected between patients with or without cytogenetic abnormalities in terms of age (50 vs. 58, P=0.337), sex ratio (male 55.56% vs. 62.10%, female 44.44% vs. 37.90%, P=0.762), or episode of acute aplastic anemia (44.44% vs. 37.10%, P=0.728). Patients with cytogenetic abnormalities had a tendency towards poorer rate of therapeutic response, which was however not significantly different from those without (55.56% vs. 79.03%, P=0.116). All of the 4 patients with +8 responded to treatment, whilst none of those with -7 or 7q- did. CONCLUSION: No significant difference was found between aplastic anemia patients with or without cytogenetic abnormalities in terms of clinical features and therapeutic response. Patients with trisomy 8 seem to have a favorable response towards treatment.