Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Nong Lin¹ , Qiaolu Yang¹, Tong Xu², Lianguo Shi³

¹Department of Breast Surgery; ²Department of Internal Medicine-Oncology; ³Department of Pathology, First Affiliated Hospital of Xiamen University, Xiamen City, Fujian Province 361000, China.

For correspondence:- Nong Lin Email: NongLinfjk@163.com Tel:+865922137512

Accepted: 30 January 2020 Published: 29 February 2020

Citation: Lin N, Yang Q, Xu T, Shi L. Evaluation of chidamide and PFI-1 as a combination therapy for triple-negative breast cancer. Trop J Pharm Res 2020; 19(2):259-264 doi: 10.4314/tjpr.v19i2.7

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

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 triple-negative 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 three-dimensional 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