Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2018; 9:21629.

Chidamide and decitabine can synergistically induce apoptosis of Hodgkin lymphoma cells by up-regulating the expression of PU.1 and KLF4

Tao Jiang, Fujue Wang, Lianjie Hu, Xiaomin Cheng, Yuhuan Zheng, Ting Liu and Yongqian Jia _

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Oncotarget. 2017; 8:77586-77594. https://doi.org/10.18632/oncotarget.20659

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Abstract

Tao Jiang1,2, Fujue Wang1,4, Lianjie Hu1,4, Xiaomin Cheng1,3, Yuhuan Zheng1,4, Ting Liu1,4 and Yongqian Jia1,4

1Department of Hematology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China

2Department of Hematology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu 610072, Sichuan, China

3Department of Hematology, Chengdu Military General Hospital, Chengdu 610083, Sichuan, China

4Laboratory of Hematology, West China Hospital of Sichuan University, Tianfu Life Science Park, Chengdu 610041, Sichuan, China

Correspondence to:

Yongqian Jia, email: [email protected]

Keywords: Hodgkin lymphoma, chidamide, decitabine, epigenetic regulation, synergistic

Received: January 16, 2017     Accepted: July 25, 2017     Published: September 06, 2017

ABSTRACT

Epigenetic abnormalities play important roles in the pathogenesis of Hodgkin lymphoma (HL). Highly expressed class I histone acetyltransferase (HDAC) and hyper-methylation of the promoter region of tumor suppressor genes have been demonstrated in Hodgkin lymphoma. In this paper, we investigated the synergistic effects of combination treatment of chidamide, a selective HDAC inhibitor, and decitabine, a demethylation agent, for HL cell lines and explored a new strategy for treating HL. The apoptosis rates, cell cycle, mitochondrial transmembrane potentials, epigenetic changes and gene expression of HL cell lines treated with chidamide as a single agent and in combination with decitabine were tested. We found that chidamide inhibited the proliferation of HL cells through increased apoptosis. Interestingly, after combined with decitabine, the inhibition rate and apoptotic death in HL cells were significantly increased. Further studies demonstrated that when combined with decitabine the expression of acetylated histone H3 and H3K9 induced by chidamide in HL cells increased, and also the expression of tumor suppressor genes PU.1 and KLF4, which exert inhibition through apoptosis pathway. Therefore, we could come to a conclusion that chidamide and decitabine can synergistically induce apoptosis of Hodgkin lymphoma cells by up-regulating the expression of PU.1 and KLF4. These results provide a new sight in combining two different epigenetic regulatory agents for treating HL.


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