The inhibitory effects of suberoylanilide hydroxamic acid on the malignant phenotypes of ovarian carcinoma cells / 天津医药

ABSTRACT

Objective To explore the effects and molecular mechanisms of suberoylanilide hydroxamic acid (SAHA) on ovarian carcinoma. Methods (1)Two groups of ovarian carcinoma cell lines (SKOV3 and SKOV3/DDP, HO8910 and HO8910-PM) were exposed to SAHA (1, 3, 5 and 7μmol/L SAHA,group 1-group 4). CCK-8 method was employed to eval-uate the inhibitory effects of SAHA.(2)Ovarian cancer cell lines treated with SAHA (2 or 5μmol/L SAHA) were used as 1 and 2 groups. Flow cytometry was performed following staining with Annexin V-FITC and PI for cell cycle and apoptosis.(3) Reverse transcription polymerase chain reaction (RT-PCR) and Western blot assay were used to assess the mRNA and pro-tein expression levels of phenotypic correlation factor. Results (1)After 48 h of SAHA treatment,the OD value of SKOV3, SKOV3/DDP,and HO8910 showed a trend of gradually reduce (P<0.05).(2)The apoptotic rates were significantly higher in SAHA 1 and SAHA 2 groups than those of control group (P<0.05). Compared with control group, after 48 h of SAHA treat-ment,S phase and G2/M phase of SKOV3 and SKOV3/DDP cells increased;G0/G1 phase of HO8910 and HO8910-PM cells increased in SAHA 1 and 2 groups (P<0.05).(3)The expression levels of CyclinB1 and Cdc2 (p34) mRNA were significant-ly lower in SAHA 1 and 2 groups than those of control group,while the expression levels of Caspase-3,p21 and p53 mRNA expression were significantly higher in SAHA 1 and 2 groups than those of control group. Furthermore,the expression of Ac-Histone H3,Ac-Histone H4,p53 protein were markedly improved,and CyclinB1,Cdc2(p34) protein decreased in SAHA 1-4 groups. Conclusion SAHA may suppress cell growth, induce apoptosis and cause cycle arrest in ovarian carcinoma cells by promoting histone acetylation or modulating their phenotype-related proteins of Caspase-3, p53, CyclinB1 and Cdc2(p34).