TY - JOUR
T1 - Chidamide Reverses Fluzoparib Resistance in Triple-Negative Breast Cancer Cells
AU - Li, Xinyang
AU - Yuan, Xiang
AU - Wang, Ziming
AU - Li, Jing
AU - Liu, Zhiwei
AU - Wang, Yukun
AU - Wei, Limin
AU - Li, Yuanpei
AU - Wang, Xinshuai
N1 - Funding Information:
This work was supported in part by Medical Science and Technology project grants of Henan Province (LHGJ20200576).
Publisher Copyright:
Copyright © 2022 Li, Yuan, Wang, Li, Liu, Wang, Wei, Li and Wang.
PY - 2022/2/18
Y1 - 2022/2/18
N2 - Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance is a new challenge for antitumor therapy. The purpose of this study was to investigate the reversal effects of chidamide on fluzoparib resistance, a PARPi, and its mechanism of action. A fluzoparib-resistant triple-negative breast cancer (TNBC) cell line was constructed, and the effects of chidamide and fluzoparib on drug-resistant cells were studied in vitro and in vivo. The effects of these drugs on cell proliferation, migration, invasiveness, the cell cycle, and apoptosis were detected using an MTT assay, wound-healing and transwell invasion assays, and flow cytometry. Bioinformatics was used to identify hub drug resistance genes and Western blots were used to assess the expression of PARP, RAD51, MRE11, cleaved Caspase9, and P-CDK1. Xenograft models were established to analyze the effects of these drugs on nude mice. In vivo results showed that chidamide combined with fluzoparib significantly inhibited the proliferation, migration, and invasiveness of drug-resistant cells and restored fluzoparib sensitivity to drug-resistant cells. The combination of chidamide and fluzoparib significantly inhibited the expression of the hub drug resistance genes RAD51 and MRE11, arrested the cell cycle at the G2/M phase, and induced cell apoptosis. The findings of this work show that chidamide combined with fluzoparib has good antineoplastic activity and reverses TNBC cell resistance to fluzoparil by reducing the expression levels of RAD51 and MRE11.
AB - Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance is a new challenge for antitumor therapy. The purpose of this study was to investigate the reversal effects of chidamide on fluzoparib resistance, a PARPi, and its mechanism of action. A fluzoparib-resistant triple-negative breast cancer (TNBC) cell line was constructed, and the effects of chidamide and fluzoparib on drug-resistant cells were studied in vitro and in vivo. The effects of these drugs on cell proliferation, migration, invasiveness, the cell cycle, and apoptosis were detected using an MTT assay, wound-healing and transwell invasion assays, and flow cytometry. Bioinformatics was used to identify hub drug resistance genes and Western blots were used to assess the expression of PARP, RAD51, MRE11, cleaved Caspase9, and P-CDK1. Xenograft models were established to analyze the effects of these drugs on nude mice. In vivo results showed that chidamide combined with fluzoparib significantly inhibited the proliferation, migration, and invasiveness of drug-resistant cells and restored fluzoparib sensitivity to drug-resistant cells. The combination of chidamide and fluzoparib significantly inhibited the expression of the hub drug resistance genes RAD51 and MRE11, arrested the cell cycle at the G2/M phase, and induced cell apoptosis. The findings of this work show that chidamide combined with fluzoparib has good antineoplastic activity and reverses TNBC cell resistance to fluzoparil by reducing the expression levels of RAD51 and MRE11.
KW - chidamide
KW - drug resistance reversal
KW - fluzoparib
KW - PARP inhibitor resistance
KW - triple-negative breast cancer
UR - http://www.scopus.com/inward/record.url?scp=85125696856&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85125696856&partnerID=8YFLogxK
U2 - 10.3389/fonc.2022.819714
DO - 10.3389/fonc.2022.819714
M3 - Article
AN - SCOPUS:85125696856
VL - 12
JO - Frontiers in Oncology
JF - Frontiers in Oncology
SN - 2234-943X
M1 - 819714
ER -