1. Dexamethasone-tamoxifen combination exerts synergistic therapeutic effects in tamoxifen-resistance breast cancer cells.
- Author
-
Gaballah AI, Elsherbiny AA, Sharaky M, Hamed NO, Raslan NA, Almilaibary A, Fayyad RMA, Ousman MS, Hamdan AME, and Fahim SA
- Subjects
- Humans, Female, MCF-7 Cells, Apoptosis drug effects, Cell Movement drug effects, Wnt Signaling Pathway drug effects, Gene Expression Regulation, Neoplastic drug effects, Antineoplastic Agents, Hormonal pharmacology, Antineoplastic Combined Chemotherapy Protocols pharmacology, Cell Line, Tumor, E2F3 Transcription Factor metabolism, E2F3 Transcription Factor genetics, SOXB1 Transcription Factors metabolism, SOXB1 Transcription Factors genetics, Tamoxifen pharmacology, Dexamethasone pharmacology, Drug Resistance, Neoplasm drug effects, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Breast Neoplasms pathology, Breast Neoplasms genetics, Drug Synergism, Cell Proliferation drug effects
- Abstract
Tamoxifen (TAM) is a key player in estrogen receptor-positive (ER+) breast cancer (BC); however, ∼30% of patients experience relapse and a lower survival rate due to TAM resistance. TAM resistance was related to the over expression of SOX-2 gene, which is regulated by the E2F3 transcription factor in the Wnt signaling pathway. It was suggested that SOX-2 overexpression was suppressed by dexamethasone (DEX), a glucocorticoid commonly prescribed to BC patients. The aim of the present study is to explore the effect of combining DEX and TAM on the inhibition of TAM-resistant LCC-2 cells (TAMR-1) through modulating the E2F3/SOX-2-mediated Wnt signaling pathway. The effect of the combination therapy on MCF-7 and TAMR-1 cell viability was assessed. Drug interactions were analyzed using CompuSyn and SynergyFinder softwares. Cell cycle distribution, apoptotic protein expression, gene expression levels of SOX-2 and E2F3, and cell migration were also assessed. Combining DEX with TAM led to synergistic inhibition of TAMR-1 cell proliferation and migration, induced apoptosis, reduced SOX-2 and E2F3 expression and was also associated with S and G2-M phase arrest. Therefore, combining DEX with TAM may present an effective therapeutic option to overcome TAM resistance, by targeting the E2F3/SOX-2/Wnt signaling pathway, in addition to its anti-inflammatory effect., (© 2024 The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF