CXCR4 Antagonist AMD3100 Reverses the Resistance to Tamoxifen in Breast Cancer via Inhibiting AKT Phosphorylation

Molecular Therapy Oncolytics
Jun ZhouTao Huang

Abstract

Endocrine therapy is a systemic therapy and has become the main treatment strategy for patients with estrogen receptor (ER)-positive breast cancer. However, tamoxifen resistance has become an insurmountable clinical challenge, and the underlying mechanisms are still poorly understood. In this study, we explored the roles of CXC chemokine receptor type 4 (CXCR4) in tamoxifen-treated breast cancer and tamoxifen resistance. Based on the Gene Expression Omnibus (GEO) database, high expression of CXCR4 was found to be associated with worse overall survival (hazard ratio [HR] = 4.646, p < 0.001) and cancer-specific survival (HR = 4.480, p < 0.001) in tamoxifen-treated breast cancer. CXCR4 was also positively correlated with the level of AKT phosphorylation and the resistance to tamoxifen in breast cancer. AMD3100 is a CXCR4 antagonist and was found to decrease phosphorylated (p)-AKT levels of tamoxifen-resistant cells. The reversal effect of AMD3100 on tamoxifen resistance was also confirmed in vitro and in vivo. Taken together, our study demonstrated that CXCR4 could be a potential prognostic biomarker for tamoxifen-treated breast cancer, and the combination of AMD3100 with tamoxifen could be a more efficacious therapeutic strategy ...Continue Reading

Citations

Jan 21, 2021·International Journal of Molecular Sciences·Jan KorbeckiIrena Baranowska-Bosiacka
Jun 8, 2021·Molecular Therapy Oncolytics·Xiao-Li YangDa Fu

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Datasets Mentioned

BETA
GSE129544
GSE9893
and
GSE31831

Methods Mentioned

BETA
PCR
transfection
xenograft
Assay
Protein Assay
electrophoresis

Software Mentioned

R
R package “ ggplot2
survivalROC
GraphPad Prism
SPSS

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