Egr-1 Enhances Drug Resistance of Breast Cancer Cells by MDR1 Dependence

Paclitaxel (PTX) is one of the most effective drugs used in the treatment of breast cancer. Nonetheless, the appearance of MDR1 (multidrug resistance 1) in tumor cells has become a significant hindrance for efficacious chemotherapy. In this study, we show that the expression level of Egr-1 (early gr...

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Bibliographic Details
Published inBrazilian Journal of Pharmaceutical Sciences Vol. 59
Main Author Gong, Pei-yao
Format Journal Article
LanguageEnglish
Published Sao Paulo Universidade de Sao Paulo Faculdade de Ciencias 01.01.2023
Universidade de São Paulo, Faculdade de Ciências Farmacêuticas
Universidade de São Paulo
Subjects
Antibodies
Breast cancer
Cancer therapies
Cell growth
Chemotherapy
Drug resistance
Egr-1
Genes
Glycoproteins
Growth factors
Hormones
MDR1
Membranes
PHARMACOLOGY & PHARMACY
Proteins
Beijing China
United States > US
China
Egr-1
MDR1
Breast cancer
Drug resistance
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Summary:Paclitaxel (PTX) is one of the most effective drugs used in the treatment of breast cancer. Nonetheless, the appearance of MDR1 (multidrug resistance 1) in tumor cells has become a significant hindrance for efficacious chemotherapy. In this study, we show that the expression level of Egr-1 (early growth response gene-1) in cancer tissues (from paclitaxel chemotherapy failure patients) and MCF-7/PTX cells (the breast cancer cell line that was resistant to paclitaxel) was increased. Cell proliferation assay and apoptosis assay revealed that Egr-1 could promote cell growth and inhibit apoptosis in MCF-7/PTX. Mechanistic studies indicated that Egr-1 could bind to the proximal MDR1 promoter and enhance MDR1 transcription. These findings indicate that paclitaxel induced Egr-1 accumulation and upregulated the expression of MDR1, thereby inducing the drug resistance in MCF-7/PTX. Our results suggest a novel pathway by which paclitaxel induces MDR1 expression, possibly illuminating a potential target pathway for the prevention of MDR1-mediated drug resistance.
ISSN:2175-9790
1984-8250
2175-9790
DOI:10.1590/s2175-97902023e18705