Effects of suberoylanilide hydroxamic acid (SAHA) combined with paclitaxel (PTX) on paclitaxel-resistant ovarian cancer cells and insights into the underlying mechanisms

Cancer Cell International

Yi Zhang²  Yue Zhao¹  Chundong Li¹  Huaping Liu¹  Yuanlin Liu²  Ying Tong¹  Zhaohui Liu¹ 

[1] Department of Obstetrics and Gynecology, Air Force General Hospital, Beijing 100142, China;Department of Cell Biology, Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing 100850, China

关键词: Chemotherapy;    Resistance;    Cell-cycle arrest;    Apoptosis;    Antitumor;    Synergistic;    Paclitaxel;    Histone deacetylase inhibitors;    Suberoylanilide hydroxamic acid;   

Others  :  1171068
DOI  :  10.1186/s12935-014-0112-x

 received in 2014-04-21, accepted in 2014-10-22,  发布年份 2014

【 摘 要 】

Background

Suberoylanilide hydroxamic acid (SAHA) is a member of the hydroxamic acid class of the newly developed histone deacetylase inhibitors. Recently, Suberoylanilide hydroxamic acid has attracted increasing attention because of its antitumor activity and synergistic effects in combination with a variety of traditional chemotherapeutic drugs. Paclitaxel (PTX), is a natural anticancer drugs; however, resistance to paclitaxel has become a major challenge to the efficacy of this agent. The purpose of this study was to investigate the effects of the combined application of these two drugs on the paclitaxel-resistant ovarian cancer OC3/P cell line.

Methods

In the present study, the effects of Suberoylanilide hydroxamic acid or/and paclitaxel on OC3/P cells cultured in vitro were analyzed in terms of cell viability, migration, cell-cycle progression and apoptosis by CCK-8, wound healing and flow cytometry assays. Changes in cell ultrastructure were observed by transmission electron microscopy. The expression of genes and proteins related to proliferation, apoptosis and drug resistance were analyzed by quantitative real-time polymerase chain reaction and Western blot analyses.

Results

There was no cross-resistance of the paclitaxel-resistant ovarian cancer OC3/P cells to Suberoylanilide hydroxamic acid. Suberoylanilide hydroxamic acid combined with paclitaxel significantly inhibited cell growth and reduced the migration of OC3/P cells compared with the effects of Suberoylanilide hydroxamic acid or paclitaxel alone. Q-PCR showed the combination of Suberoylanilide hydroxamic acid and paclitaxel reduced intracellular bcl-2 and c-myc gene expression and increased bax gene expression more distinctly than the application of SAHA or paclitaxel alone. Moreover, the level of mdr1 gene expression in cells treated with Suberoylanilide hydroxamic acid was lower than that of the control group (P <0.05). Western blot analysis showed that Suberoylanilide hydroxamic acid alone or in combination with paclitaxel enhanced caspase-3 protein expression and degraded ID1 protein expression in OC3/P cells.

Conclusion

Suberoylanilide hydroxamic acid inhibited the growth of paclitaxel-resistant ovarian cancer OC3/P cells and reduced migration by the induction of cell-cycle arrest, apoptosis and autophagy. These observations indicate the possible synergistic antitumor effects of sequential Suberoylanilide hydroxamic acid and paclitaxel treatment.

【 授权许可】

   
2014 Liu et al.; licensee BioMed Central Ltd.

【 图 表 】

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