Chidamide Reverses Fluzoparib Resistance in Triple-Negative Breast Cancer Cells
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 (TNB...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-02-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.819714/full |
| _version_ | 1818974754938290176 |
|---|---|
| author | Xinyang Li Xiang Yuan Ziming Wang Jing Li Zhiwei Liu Yukun Wang Limin Wei Yuanpei Li Xinshuai Wang |
| author_facet | Xinyang Li Xiang Yuan Ziming Wang Jing Li Zhiwei Liu Yukun Wang Limin Wei Yuanpei Li Xinshuai Wang |
| author_sort | Xinyang Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T15:45:05Z |
| format | Article |
| id | doaj.art-919b061958334fe09661d37b1a99c83e |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T15:45:05Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-919b061958334fe09661d37b1a99c83e2022-12-21T19:34:59ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-02-011210.3389/fonc.2022.819714819714Chidamide Reverses Fluzoparib Resistance in Triple-Negative Breast Cancer CellsXinyang Li0Xiang Yuan1Ziming Wang2Jing Li3Zhiwei Liu4Yukun Wang5Limin Wei6Yuanpei Li7Xinshuai Wang8Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, ChinaHenan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, ChinaHenan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, ChinaHenan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, ChinaHenan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, ChinaHenan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, ChinaHenan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, ChinaDepartment of Internal Medicine, UC Davis Comprehensive Cancer Center, University of California, Davis, Sacramento, CA, United StatesHenan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, ChinaPoly (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.https://www.frontiersin.org/articles/10.3389/fonc.2022.819714/fulltriple-negative breast cancerPARP inhibitor resistancedrug resistance reversalfluzoparibchidamide |
| spellingShingle | Xinyang Li Xiang Yuan Ziming Wang Jing Li Zhiwei Liu Yukun Wang Limin Wei Yuanpei Li Xinshuai Wang Chidamide Reverses Fluzoparib Resistance in Triple-Negative Breast Cancer Cells Frontiers in Oncology triple-negative breast cancer PARP inhibitor resistance drug resistance reversal fluzoparib chidamide |
| title | Chidamide Reverses Fluzoparib Resistance in Triple-Negative Breast Cancer Cells |
| title_full | Chidamide Reverses Fluzoparib Resistance in Triple-Negative Breast Cancer Cells |
| title_fullStr | Chidamide Reverses Fluzoparib Resistance in Triple-Negative Breast Cancer Cells |
| title_full_unstemmed | Chidamide Reverses Fluzoparib Resistance in Triple-Negative Breast Cancer Cells |
| title_short | Chidamide Reverses Fluzoparib Resistance in Triple-Negative Breast Cancer Cells |
| title_sort | chidamide reverses fluzoparib resistance in triple negative breast cancer cells |
| topic | triple-negative breast cancer PARP inhibitor resistance drug resistance reversal fluzoparib chidamide |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.819714/full |
| work_keys_str_mv | AT xinyangli chidamidereversesfluzoparibresistanceintriplenegativebreastcancercells AT xiangyuan chidamidereversesfluzoparibresistanceintriplenegativebreastcancercells AT zimingwang chidamidereversesfluzoparibresistanceintriplenegativebreastcancercells AT jingli chidamidereversesfluzoparibresistanceintriplenegativebreastcancercells AT zhiweiliu chidamidereversesfluzoparibresistanceintriplenegativebreastcancercells AT yukunwang chidamidereversesfluzoparibresistanceintriplenegativebreastcancercells AT liminwei chidamidereversesfluzoparibresistanceintriplenegativebreastcancercells AT yuanpeili chidamidereversesfluzoparibresistanceintriplenegativebreastcancercells AT xinshuaiwang chidamidereversesfluzoparibresistanceintriplenegativebreastcancercells |