Establishment and characterization of a triple negative basal-like breast cancer cell line with multi-drug resistance

Establishment and characterization of a triple negative basal-like breast cancer cell line with multi-drug resistance

Triple-negative breast carcinoma (TNBC) is one of the most aggressive subtypes of breast cancer and is associated with an unfavorable prognosis. The management of TNBC is currently based on the use of classical cytotoxic drugs, i.e., anthracyclines and/or microtubule-binding agents (TBAs). However,...

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Published in:Oncology letters Vol. 14; no. 4; pp. 5039 - 5045
Main Authors: Boichuk, Sergei, Galembikova, Aigul, Sitenkov, Alexandr, Khusnutdinov, Ramil, Dunaev, Pavel, Valeeva, Elena, Usolova, Natalia
Format: Journal Article
Language:English
Published: Greece Spandidos Publications UK Ltd 01-10-2017
D.A. Spandidos
Subjects:
Apoptosis
Biotechnology
Breast cancer
Cancer therapies
Cell cycle
Cell growth
Chemotherapy
Cytotoxicity
Drug resistance
Gene expression
Genotype & phenotype
Glycoproteins
Immunoglobulins
Oncology
Polymerase chain reaction
Proteins
United States > US
P-glycoprotein
paclitaxel
apoptosis
chemoresistance
triple negative basal-like breast cancer
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Summary:Triple-negative breast carcinoma (TNBC) is one of the most aggressive subtypes of breast cancer and is associated with an unfavorable prognosis. The management of TNBC is currently based on the use of classical cytotoxic drugs, i.e., anthracyclines and/or microtubule-binding agents (TBAs). However, conventional chemotherapy is not always effective in these tumors and a systemic relapse is often observed, potentially due to the development of multi-drug resistance (MDR). Therefore, an improved understanding of MDR mechanisms may improve the therapeutic strategies for TNBC. In the present study, a paclitaxel-resistant (TxR) breast cancer cell subline of HCC1806 TNBC cells was established and characterized. The resistance index of this subline was calculated according to the IC of HCC1806-TxR relative to the parental HCC1806 cells (16.86-fold). TxR-cells also exhibited cross-resistance to vinblastin, doxorubicin and etoposide (~14-, ~4- and ~3-fold, respectively). As assessed with reverse transcription-quantitative polymerase chain reaction, TxR-resistant cells exhibited the upregulated expression of a number of multidrug resistance-associated genes, including MDR-1, MRP-1, -5, -6 and YB-1. The TxR cells also exhibited an increased expression of MDR-related proteins including MDR1 and MRP-1, which led to a substantial increase (5.4-fold) of the paclitaxel efflux from TxR-cells. In addition, the pro-apoptotic protein Fas was downregulated, whereas the anti-apoptotic Bcl-2 was upregulated, in TxR-cells. This may explain why a reduced extent of apoptosis was observed when TxR cells were exposed to TBAs and topoisomerase type II inhibitors, relative to the parental HCC1806 cells. Thus, the HCC1806-TxR cell line may serve as an appropriate model for the analysis of chemoresistance mechanisms in TNBCs, and for the investigation of novel anticancer agents for overcoming MDR-mediated mechanisms in TNBC.
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ISSN:1792-1074
1792-1082
DOI:10.3892/ol.2017.6795