Superior activity of a modified histone deacetylase inhibitor in inhibiting growth of human gastric cells by promoting p21WAF1 expression

被引：0
作者：
Ma, Lan-Ying [1 ]
Han, Mei [1 ]
Qu, Yan-Li [1 ]
Wang, Hua [2 ]
Tang, Yong [1 ]
机构：
[1] Xinjiang Med Univ, Tumor Hosp Affiliated, Dept Gastroenterol, 789Suzhou East St, Urumqi 830000, Xinjiang, Peoples R China
[2] Xinjiang Med Univ, Coll Basic Med, Urumqi 830000, Xinjiang, Peoples R China
来源：
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE | 2016年 / 9卷 / 10期
关键词：
Histone deacetylase inhibitor; gastric cancer; p21(WAF1); anticancer; INDUCED APOPTOSIS; HDAC INHIBITORS; CYCLE ARREST; CANCER; ACETYLATION; BCL-2; GENE; DIFFERENTIATION; VORINOSTAT; SIGNATURE;
D O I：
暂无
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Objective: To investigate the application of a modified histone deacetylase inhibitor named D3 for inhibiting cancer cell proliferation and inducing apoptosis. Material and methods: We designed to investigate its exact mechanism of D3 anti-cancer function. Activity of D3 against human gastric cancer cells (BGC-823, SGC-7901) and normal gastric epithelial cell line (GES-1) were investigated in vitro by using proliferation assays, cell cycle assays, apoptosis assays, RNA interference, promoter acetylation assays, as well as analysis of related molecules. Result: D3 strongly inhibited the proliferation of gastric cancer cells compared with SAHA. The 50% growth-inhibitory concentrations of D3 for GES-1, BGC-823, SGC-7901 treated for 48 h were 3.2 +/- 0.09 mu M, 3.77 +/- 0.1 mu M, 4.97 +/- 0.2 mu M while that of SAHA were 12.9 +/- 0.26 mu M, 28.93 +/- 0.4 mu M, 27.1 +/- 0.4 mu M respectively. We found that D3 caused more significant G1 cell cycle arrest and apoptosis than SAHA in a density-dependent manner. In addition, levels of Bcl-xl and Bcl-2 mRNA and protein in BGC823 cells decreased after treatment with either SAHA or D3; moreover, D3 had a higher inhibition activity. D3 induced hyperacetylation of histone H3 and H4 around the promoter region of p21(WAF1). Conclusion: D3 could represent a novel pharmacological agent with potential benefit for patients with gastric cancer.
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页码：20212 / 20223
页数：12
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