The effects of a histone deacetylase inhibitor on biological behavior of diffuse large B-cell lymphoma cell lines and insights into the underlying mechanisms

Cancer Cell International

Xiaoyan Zhou²  Rui Bi²  Ping Zhang¹  Yayun Chi¹  Ping Wei²  Weixiang Chen²  Wenli Cui²  Ying Cai² 

[1] Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai, PR China;Institute of Pathology, Fudan University, Shanghai, PR China

关键词: p53;    Akt pathway;    Trichostatin A;    HDAC;    Diffuse large B-cell lymphoma;   

Others  :  793630
DOI  :  10.1186/1475-2867-13-57

 received in 2012-12-27, accepted in 2013-05-28,  发布年份 2013

【 摘 要 】

Background

Epigenetic control using histone deacetylase (HDAC) inhibitors is a promising therapy for lymphomas. Insights into the anti-proliferative effects of HDAC inhibitors on diffuse large B-cell lymphoma (DLBCL) and further understanding of the underlying mechanisms, which remain unclear to date, are of great importance.

Methods

Three DLBCL cell lines (DoHH2, LY1 and LY8) were used to define the potential epigenetic targets for Trichostatin A (TSA)-mediated anti-proliferative effects via CCK-8 assay. Cell cycle distribution and apoptosis were detected by flow cytometry. We further investigated the underlying molecular mechanisms by examining expression levels of relevant proteins using western blot analysis.

Results

TSA treatment inhibited the growth of all three DLBCL cell lines and enhanced cell cycle arrest and apoptosis. Molecular analysis revealed upregulated acetylation of histone H3, α-tubulin and p53, and dephosphorylation of pAkt with altered expression of its main downstream effectors (p21, p27, cyclin D1 and Bcl-2). HDAC profiling revealed that all three cell lines had varying HDAC1–6 expression levels, with the highest expression of all six isoforms, in DoHH2 cells, which displayed the highest sensitivity to TSA.

Conclusion

Our results demonstrated that the HDAC inhibitor TSA inhibited DLBCL cell growth, and that cell lines with higher expression of HDACs tended to be more sensitive to TSA. Our data also suggested that inhibition of pAkt and activation of p53 pathway are the main molecular events involved in inhibitory effects of TSA.

【 授权许可】

   
2013 Cai et al.; licensee BioMed Central Ltd.

【 图 表 】

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