| Autor: |
Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
npj Precision Oncology, Vol 7, Iss 1, Pp 1-14 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2397-768X |
| DOI: |
10.1038/s41698-023-00422-8 |
| Popis: |
Abstract Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes. Adaptive alterations in gene expression were analyzed and validated in additional CL TNBC cells. Tumor xenograft models were used to test the in vivo antitumor activity of panobinostat alone or its combinations with gefitinib, an EGFR-tyrosine kinase inhibitor (TKI). Panobinostat potently inhibited proliferation and induced apoptosis in all TNBC cells tested. However, in CL TNBC cells, this HDAC inhibitor markedly enhanced expression of HER3, which interacted with EGFR to activate both receptors and Akt signaling pathways. Combinations of panobinostat and gefitinib synergistically suppressed CL TNBC cell proliferation and promoted apoptosis in vitro and in vivo. Upregulation of HER3 compromises the efficacy of panobinostat in CL TNBC. Inactivation of HER3 combined with panobinostat represents a practical approach to combat CL TNBC. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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