Dexamethasone-tamoxifen Combination Exerts Synergistic Therapeutic Effects in Tamoxifen-resistance Breast Cancer Cells

Overview

Journal Biosci Rep

Specialty Cell Biology

Date 2024 Jun 12

PMID 38864530

Authors

Aliaa I Gaballah

Aliaa A Elsherbiny

Marwa Sharaky

Najat O Hamed

Nahed A Raslan

Abdullah Almilaibary

Reda Mohamed Abdrabbou Fayyad

Mona S Ousman

Ahmed M E Hamdan

Sally A Fahim

Affiliations

Soon will be listed here.

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.

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