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

基因表达改变对三阴性乳腺癌细胞阿霉素耐药性影响的新见解

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作者:Cristina Alexandra Ciocan-Cartita, Ancuta Jurj, Oana Zanoaga, Roxana Cojocneanu, Laura-Ancuta Pop, Alin Moldovan, Cristian Moldovan, Alina Andreea Zimta, Lajos Raduly, Cecilia Pop-Bica, Mihail Buse, Liviuta Budisan, Piroska Virag, Alexandru Irimie, Sandra Martha Gomes Dias, Ioana Berindan-Neagoe, Co

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

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.

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.

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