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JCR 2016
جستجوی مقالات
جمعه 21 آذر 1404
Research in Pharmaceutical Sciences
، جلد ۱۹، شماره ۵، صفحات ۶۰۶-۶۲۱
عنوان فارسی
چکیده فارسی مقاله
کلیدواژههای فارسی مقاله
عنوان انگلیسی
The activation of the G-protein-coupled estrogen receptor promotes the aggressiveness of MDA-MB231 cells by targeting the IRE1α/TXNIP pathway
چکیده انگلیسی مقاله
Background and purpose: This study investigated modulating the G protein-coupled estrogen receptor (GPER) on the IRE1α/TXNIP pathway and its role in drug resistance in MDA-MB231 cells. Experimental approach: To determine the optimal concentrations of G 1 and 4-hydroxytamoxifen (TAM), GPER expression and ERK1/2 phosphorylation were analyzed using qRT-PCR and western blotting, respectively. Cells were treated with individual concentrations of G 1 (1000 nM), G 15 (1000 nM), and TAM (2000 nM), as well as combinations of these treatments (G 1 + G 15 , TAM + G 15 , and G 1 + TAM) for 24 and 48 h. The expression levels of GPER, IRE1α, miR-17-5p, TXNIP, ABCB1, and ABCC1 genes and TXNIP protein expression were evaluated. Finally, apoptosis and cell migration were examined using flow cytometry and the wound-healing assay, respectively. Findings/Results: Activating GPER with its specific agonist G 1 and TAM significantly increased IRE1α levels in MDA-MB231 cells. IRE1α through splicing XBP1 led to unfolded protein response. In addition, decreased TXNIP gene and protein expression reduced apoptosis, increased migration, and upregulated the genes associated with drug resistance. Conclusion and implication: Our investigation revealed that blocking the GPER/IRE1α/TXNIP pathway in MDA-MB231 cells could enhance treatment efficacy and improve chemotherapy responsiveness. The distinct unfolded protein response observed in MDA-MB231 cells may stem from the unique characteristics of these cells, which lack receptors for estrogen, progesterone, and HER2/neu hormones, possessing only the GPER receptor (ER - /PR - /HER2 - /GPER + ). This study introduced a new pathway in TNBC cells, indicating that targeting GPER could be crucial in comprehensive therapeutic strategies in TNBC cells.
کلیدواژههای انگلیسی مقاله
Breast cancer,Drug resistance,G protein-coupled estrogen receptor,miR-17-5P,Thioredoxin interacting protein,Unfolded protein response.
نویسندگان مقاله
| Maryam Mohammad-Sadeghipour
Applied Cellular and Molecular Research Center, Kerman University of Medical Sciences, Kerman, Iran.
| Mohammad Hadi Nematollahi
3Department of Epidemiology and Biostatistics, School of Health, Occupational Environment Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
| Hassan Ahmadinia
Molecular Medicine Research Center, Institute of Basic Medical Sciences Research, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. Department of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
| Mohammad Reza Hajizadeh
Department of Clinical Biochemistry, Afzalipoor Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran. Molecular Medicine Research Center, Institute of Basic Medical Sciences Research, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
| Mehdi Mahmoodi
نشانی اینترنتی
http://rps.mui.ac.ir/index.php/jrps/article/view/2276
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Original Article
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