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

Abstract 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...

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Main Author: Pei-yao Gong
Format: Article
Language:English
Published: Universidade de São Paulo 2023-08-01
Series:Brazilian Journal of Pharmaceutical Sciences
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502023000100397&lng=en&tlng=en
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author Pei-yao Gong
author_facet Pei-yao Gong
author_sort Pei-yao Gong
collection DOAJ
description Abstract 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.
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spelling doaj.art-3470133069504fd1afbc96324912a5712023-08-29T07:45:03ZengUniversidade de São PauloBrazilian Journal of Pharmaceutical Sciences2175-97902023-08-015910.1590/s2175-97902023e18705Egr-1 Enhances Drug Resistance of Breast Cancer Cells by MDR1 DependencePei-yao Gonghttps://orcid.org/0000-0002-1355-5879Abstract 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502023000100397&lng=en&tlng=enEgr-1Breast cancerMDR1Drug resistance.
spellingShingle Pei-yao Gong
Egr-1 Enhances Drug Resistance of Breast Cancer Cells by MDR1 Dependence
Brazilian Journal of Pharmaceutical Sciences
Egr-1
Breast cancer
MDR1
Drug resistance.
title Egr-1 Enhances Drug Resistance of Breast Cancer Cells by MDR1 Dependence
title_full Egr-1 Enhances Drug Resistance of Breast Cancer Cells by MDR1 Dependence
title_fullStr Egr-1 Enhances Drug Resistance of Breast Cancer Cells by MDR1 Dependence
title_full_unstemmed Egr-1 Enhances Drug Resistance of Breast Cancer Cells by MDR1 Dependence
title_short Egr-1 Enhances Drug Resistance of Breast Cancer Cells by MDR1 Dependence
title_sort egr 1 enhances drug resistance of breast cancer cells by mdr1 dependence
topic Egr-1
Breast cancer
MDR1
Drug resistance.
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502023000100397&lng=en&tlng=en
work_keys_str_mv AT peiyaogong egr1enhancesdrugresistanceofbreastcancercellsbymdr1dependence