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http://dx.doi.org/10.7314/APJCP.2014.15.11.4663

Effect of Trichostatin A on CNE2 Nasopharyngeal Carcinoma Cells - Genome-wide DNA Methylation Alteration  

Yang, Xiao-Li (Medical Scientific Research Center, Guangxi Medical University)
Zhang, Cheng-Dong (Medical Scientific Research Center, Guangxi Medical University)
Wu, Hua-Yu (Medical Scientific Research Center, Guangxi Medical University)
Wu, Yong-Hu (Medical Scientific Research Center, Guangxi Medical University)
Zhang, Yue-Ning (Medical Scientific Research Center, Guangxi Medical University)
Qin, Meng-Bin (Medical Scientific Research Center, Guangxi Medical University)
Wu, Hua (Medical Scientific Research Center, Guangxi Medical University)
Liu, Xiao-Chun (Department of laboratories, The People's Hospital of Guangxi Zhuang Autonomous Region)
Lina, Xing (Medical Scientific Research Center, Guangxi Medical University)
Lu, Shao-Ming (Medical Scientific Research Center, Guangxi Medical University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.11, 2014 , pp. 4663-4670 More about this Journal
Abstract
Trichostatin A (TSA) is a histone deacetylase (HDAC) inhibitor. We here investigated its effects on proliferation and apoptosis of the CNE2 carcinoma cell line, and attempted to establish genome-wide DNA methylation alteration due to differentially histone acetylation status. After cells were treated by TSA, the inhibitory rate of cell proliferation was examined with a CCK8 kit, and cell apoptosis was determined by flow cytometry. Compared to control, TSA inhibited CNE2 cell growth and induced apoptosis. Furthermore, TSA was found to induce genome-wide methylation alteration as assessed by genome-wide methylation array. Overall DNA methylation level of cells treated with TSA was higher than in controls. Function and pathway analysis revealed that many genes with methylation alteration were involved in key biological roles, such as apoptosis and cell proliferation. Three genes (DAP3, HSPB1 and CLDN) were independently confirmed by quantitative real-time PCR. Finally, we conclude that TSA inhibits CNE2 cell growth and induces apoptosis in vitro involving genome-wide DNA methylation alteration, so that it has promising application prospects in treatment of NPC in vivo. Although many unreported hypermethylated/hypomethylated genes should be further analyzed and validated, the pointers to new biomarkers and therapeutic strategies in the treatment of NPC should be stressed.
Keywords
Trichostatin A; nasopharyngeal carcinoma; CNE2; methylation; acetylation;
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