Tianjin Med J ›› 2016, Vol. 44 ›› Issue (2): 149-154.doi: 10.11958/58778

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The inhibitory effects of suberoylanilide hydroxamic acid on the malignant phenotypes of ovarian carcinoma cells

CHANG Xingsheng1, ZHENG Huachuan2,ZHAO Shuang2, GOU Wenfeng2, YANG Xuefeng2 , LIU Xiaojuan1△   

  1. 1 Department of Pharmacy, Liaoning Medical University, Jinzhou 121000, China; 2 Cancer Research Center of the First Affiliated Hospital, Liaoning Medical University
  • Received:2015-04-13 Revised:2015-09-22 Published:2016-02-15 Online:2016-02-15
  • Contact: △Corresponding Author E-mail: lxj_yxy@163.com E-mail:719962257@qq.com

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 7 μmol/L SAHA, group 1-group 4). CCK-8 method was employed to evaluate the inhibitory effects of SAHA.(2) Ovarian cancer cell lines treated with SAHA (2 or 5 μmol/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 protein 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 treatment, 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 significantly 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).

Key words: ovarian neoplasms, apoptosis, cell proliferation, malignant phenotype, suberoylanilide hydroxamic acid, histone acetylationacetylation