New insights in gene expression alteration as effect of doxorubicin drug resistance in triple negative breast cancer cells
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Published:2020-11-13
Issue:1
Volume:39
Page:
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ISSN:1756-9966
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Container-title:Journal of Experimental & Clinical Cancer Research
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language:en
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Short-container-title:J Exp Clin Cancer Res
Author:
Ciocan-Cartita Cristina Alexandra, Jurj Ancuta, Zanoaga Oana, Cojocneanu Roxana, Pop Laura-Ancuta, Moldovan Alin, Moldovan Cristian, Zimta Alina Andreea, Raduly Lajos, Pop-Bica Cecilia, Buse Mihail, Budisan Liviuta, Virag Piroska, Irimie Alexandru, Gomes Dias Sandra Martha, Berindan-Neagoe Ioana, Braicu CorneliaORCID
Abstract
Abstract
Background
Triple negative breast cancer (TNBC) is a heterogeneous disease with aggressive behavior and an unfavorable prognosis rate. Due to the lack of surface receptors, TNBC must be intensely investigated in order to establish a suitable treatment for patients with this pathology. Chemoresistance is an important reason for therapeutic failure in TNBC.
Method
The aim of this study was to investigate the effect of doxorubicin in TNBC cell lines and to highlight cellular and molecular alterations after a long exposure to doxorubicin.
Results
The results revealed that doxorubicin significantly increased the half maximal inhibitory concentration (IC50) values at P12 and P24 compared to parenteral cells P0. Modifications in gene expression were investigated through microarray technique, and for detection of mutational pattern was used Next Generation Sequencing (NGS). 196 upregulated and 115 downregulated genes were observed as effect of multiple dose exposure, and 15 overexpressed genes were found to be involved in drug resistance. Also, the presence of some additional mutations in both cell lines was observed.
Conclusion
The outcomes of this research may provide novel biomarkers for drug resistance in TNBC. Also, this activity can highlight the potential mechanisms associated with drug resistance, as well as the potential therapies to counteract these mechanisms.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology
Reference39 articles.
1. Hudis CA, Gianni L. Triple-negative breast cancer: an unmet medical need. Oncologist. 2011;16(Suppl 1):1–11. https://doi.org/10.1634/theoncologist.2011-S1-01. 2. Braicu C, Raduly L, Morar-Bolba G, Cojocneanu R, Jurj A, Pop LA, Pileczki V, Ciocan C, Moldovan A, Irimie A, Eniu A, Achimas-Cadariu P, Paradiso A, et al. Aberrant miRNAs expressed in HER-2 negative breast cancers patient. J Exp Clin Cancer Res. 2018;37:257. https://doi.org/10.1186/s13046-018-0920-2. 3. Tormo E, Ballester S, Adam-Artigues A, Burgués O, Alonso E, Bermejo B, Menéndez S, Zazo S, Madoz-Gúrpide J, Rovira A, Albanell J, Rojo F, Lluch A, et al. The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factors. Scientific Rep. 2019;9:5316. https://doi.org/10.1038/s41598-019-41472-y. 4. Lajos R, Braicu C, Jurj A, Chira S, Cojocneanu-Petric R, Pileczki V, Berindan-Neagoe I. A miRNAs profile evolution of triple negative breast cancer cells in the presence of a possible adjuvant therapy and senescence inducer. J Buon. 2018;23:692–705. 5. Braicu C, Chiorean R, Irimie A, Chira S, Tomuleasa C, Neagoe E, Paradiso A, Achimas-Cadariu P, Lazar V, Berindan-Neagoe I. Novel insight into triple-negative breast cancers, the emerging role of angiogenesis, and antiangiogenic therapy. Expert Rev Mol Med. 2016;18:e18. https://doi.org/10.1017/erm.2016.17.
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