Evaluation of chidamide and PFI-1 as a combination therapy for triple-negative breast cancer

  • Nong Lin
  • Qiaolu Yang
  • Tong Xu
  • Lianguo Shi
Keywords: Triple-negative breast cancer, Histone deacetylases, Bromodomain

Abstract

Purpose: To evaluate the in vitro and in vivo effects of the combination therapy of histone deacetylases (HDAsC) inhibitor, chidamide, and bromodomain-containing proteins (BETs) inhibitor, PFI-1, on triplenegative breast cancer (TNBC).

Methods: Four distinct breast cancer cell lines and one TNBC mouse model were treated with vehicle, chidamide, PFI-1 alone, or chidamide and PFI-1. The inhibitory effect of chidamide or PFI-1 on HDACs and BETs was assessed by HDAC enzyme inhibition and AlphaScreen assays. Cell viability was determined by MTT assay while protein expression of p-STAT3 was evaluated by western blotting and immunohistochemistry (IHC) staining assay.

Results: Chidamide exerted inhibitory effect on HDACs while PFI-1 inhibited BET proteins. The threedimensional model demonstrated the interactions between chidamide and HDAC2, and between PFI-1 and BRD4. Chidamide or PFI-1 exerted inhibitory effects on breast cancer cell proliferation in vitro. However, the combination of PFI-1 and chidamide significantly inhibit MDA-MB-231 cell viability, and decrease the expression of p-STAT3, when compared to that treated with chidamide or PFI-1 alone. Moreover, the combined inhibitory effect of PFI-1 and chidamide on tumor growth was also found in the in vivo mice experiments.

Conclusion: The combination of chidamide and PFI-1 is a potential is a potential therapeutic strategy for the management of TNBC.

Keywords: Triple-negative breast cancer, Histone deacetylases, Bromodomain

Published
2020-04-09
Section
Articles

Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996