Synergistic antitumor effect of histone deacetylase inhibitor and Doxorubicin in peripheral T-cell lymphoma

Huilai Zhang, Ling Dong, Qingqing Chen, Lingzhe Kong, Bin Meng, Huaqing Wang, Kai Fu, Xi Wang, Qiang Pan-Hammarström, Ping Wang, Xianhuo Wang

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Chidamide (CS055) is a new and highly selective histone deacetylase inhibitor displaying significant single-agent activity in peripheral T-cell lymphoma (PTCL). But there is little known the synergistic effect between CS055 and chemotherapy. The purpose of this study is to explore the synergistic effect and molecular mechanisms of CS055 combination with Doxorubicin in PTCL cells. We found that CS055 showed dose- and time-dependent inhibition effects on PTCL cell. Meanwhile, the synergistic effect was significantly observed after combination treatment with lower drug-concentration of CS055 and Doxorubicin. Lower drug-concentration of CS055 induced weak apoptosis in PTCL cells, but combination treatment with CS055 and Doxorubicin promoted more significant apoptosis. Combination treatment with CS055 and Doxorubicin significantly changed mitochondrial membrane potential and H3 acetylated level, resulting in up-regulating DNA damage protein p-γH2AX and apoptosis proteins including cleaved-caspase-3, cleaved-caspase-9 and cleaved-PARP, and down-regulating anti-apoptosis protein Bcl-2. In a word, Doxorubicin could increase the CS055-induced inhibition effects on PTCL cells, suggesting that CS055 combination with Doxorubicin or Doxorubicin-based chemotherapy drugs might be a new therapy approach for PTCL patients.

Original languageEnglish (US)
Pages (from-to)29-35
Number of pages7
JournalLeukemia Research
Volume56
DOIs
Publication statusPublished - May 1 2017

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Keywords

  • Chidamide
  • Doxorubicin
  • PTCL
  • Synergistic antitumor effect

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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