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多柔比星耐药对三阴性乳腺癌细胞基因表达改变影响的新见解。

New insights in gene expression alteration as effect of doxorubicin drug resistance in triple negative breast cancer cells.

作者信息

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 Cornelia

机构信息

Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.

MedFuture Research Center for Advanced Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.

出版信息

J Exp Clin Cancer Res. 2020 Nov 13;39(1):241. doi: 10.1186/s13046-020-01736-2.

DOI:10.1186/s13046-020-01736-2
PMID:33187552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7664031/
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 (IC) 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.

摘要

背景

三阴性乳腺癌（TNBC）是一种具有侵袭性且预后不良的异质性疾病。由于缺乏表面受体，必须对TNBC进行深入研究，以便为患有这种病症的患者确立合适的治疗方法。化疗耐药是TNBC治疗失败的一个重要原因。

方法

本研究的目的是调查阿霉素对TNBC细胞系的影响，并突出长期暴露于阿霉素后的细胞和分子变化。

结果

结果显示，与亲本细胞P0相比，阿霉素在P12和P24时显著提高了半数最大抑制浓度（IC）值。通过微阵列技术研究基因表达的变化，并使用下一代测序（NGS）检测突变模式。观察到196个基因上调和115个基因下调是多剂量暴露的结果，并且发现15个过表达基因与耐药性有关。此外，在两种细胞系中均观察到一些额外突变的存在。

结论

本研究结果可能为TNBC的耐药性提供新的生物标志物。此外，该研究可以突出与耐药性相关的潜在机制，以及对抗这些机制的潜在疗法。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc48/7664031/01708361890b/13046_2020_1736_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc48/7664031/9411c0bc0036/13046_2020_1736_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc48/7664031/74d819a4bc75/13046_2020_1736_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc48/7664031/78681657af9d/13046_2020_1736_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc48/7664031/6a75f3f91cbd/13046_2020_1736_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc48/7664031/c66134760b1b/13046_2020_1736_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc48/7664031/e1d668b509ac/13046_2020_1736_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc48/7664031/c3846f170e80/13046_2020_1736_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc48/7664031/77639a0ec36d/13046_2020_1736_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc48/7664031/1f2968439f2e/13046_2020_1736_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc48/7664031/7ce19a8f237f/13046_2020_1736_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc48/7664031/01708361890b/13046_2020_1736_Fig11_HTML.jpg

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