Combination of HDAC inhibitor TSA and silibinin induces cell cycle arrest and apoptosis by targeting survivin and cyclinB1/Cdk1 in pancreatic cancer cells

被引:43
作者
Feng, Wan [1 ]
Cai, Dawei [2 ]
Zhang, Bin [1 ]
Lou, Guochun [1 ]
Zou, Xiaoping [1 ]
机构
[1] Nanjing Univ, Sch Med, Dept Gastroenterol, Affiliated Drum Tower Hosp, Nanjing 210008, Jiangsu, Peoples R China
[2] Nanjing Univ, Sch Med, Nanjing 210008, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Histone deacetylase; Silibinin; Pancreatic cancer; Combination therapy; HISTONE-DEACETYLASE INHIBITORS; GROWTH-INHIBITION; EXPRESSION; THERAPY; DEATH; B1; ADENOCARCINOMA; GEMCITABINE; EFFICACY; MITOSIS;
D O I
10.1016/j.biopha.2015.08.017
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
Histone deacetylases (HDAC) are involved in diverse biological processes and therefore emerge as potential targets for pancreatic cancer. Silibinin, an active component of silymarin, is known to inhibit growth of pancreatic cancer in vivo and in vitro. Herein, we examined the cytotoxic effects of TSA in combination with silibinin and investigated the possible mechanism in two pancreatic cancer cell lines (Panc1 and Capan2). Our study found that combination treatment of HDAC inhibitor and silibinin exerted additive growth inhibitory effect on pancreatic cancer cell. Annexin V-FITC/PI staining and flow cytometry analysis demonstrated that combination therapy induced G2/M cell cycle arrest and apoptosis in Panc1 and Capan2 cells. The induction of apoptosis was further confirmed by evaluating the activation of caspases. Moreover, treatment with TSA and silibinin resulted in a profound reduction in the expression of cyclinA2, cyclinB1/Cdk1 and survivin. Taken together, our study might indicate that the novel combination of HDAC inhibitor and silibinin could offer therapeutic potential against pancreatic cancer. (C) 2015 Published by Elsevier Masson SAS.
引用
收藏
页码:257 / 264
页数:8
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