Characterization of acquired paclitaxel resistance of breast cancer cells and involvement of ABC transporters

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F16%3A43912347" target="_blank" >RIV/00216208:11120/16:43912347 - isvavai.cz</a>

Alternative codes found

RIV/75010330:_____/16:00011486

Result on the web

<a href="http://dx.doi.org/10.1016/j.taap.2016.09.020" target="_blank" >http://dx.doi.org/10.1016/j.taap.2016.09.020</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.taap.2016.09.020" target="_blank" >10.1016/j.taap.2016.09.020</a>

Result language

angličtina

Original language name

Characterization of acquired paclitaxel resistance of breast cancer cells and involvement of ABC transporters

Original language description

Development of taxane resistance has become clinically very important issue. The molecular mechanisms underlying the resistance are still unclear. To address this issue, we established paclitaxel-resistant sublines of the SK-BR-3 and MCF-7 breast cancer cell lines that are capable of long-term proliferation in 100 nM and 300 nM paclitaxel, respectively. Application of these concentrations leads to cell death in the original counterpart cells. Both sublines are cross-resistant to doxorubicin, indicating the presence of the MDR phenotype. Interestingly, resistance in both paclitaxel-resistant sublines is circumvented by the second-generation taxane SB-T-1216. Moreover, we demonstrated that it was not possible to establish sublines of SK-BR-3 and MCF-7 cells resistant to this taxane. It means that at least the tested breast cancer cells are unable to develop resistance to some taxanes. Employing mRNA expression profiling of all known human ABC transporters and subsequent Western blot analysis of the expression of selected transporters, we demonstrated that only the ABCB1/PgP and ABCC3/MRP3 proteins were up-regulated in both paclitaxel-resistant sublines. We found up-regulation of ABCG2/BCRP and ABCC4 proteins only in paclitaxel-resistant SK-BR-3 cells. In paclitaxel-resistant MCF-7 cells, ABCB4/MDR3 and ABCC2/MRP2 proteins were up-regulated. Silencing of ABCB1 expression using specific siRNA increased significantly, but did not completely restore full sensitivity to both paclitaxel and doxorubicin. Thus we showed a key, but not exclusive, role for ABCB1 in mechanisms of paclitaxel resistance. It suggests the involvement of multiple mechanisms in paclitaxel resistance in tested breast cancer cells.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Toxicology and Applied Pharmacology

ISSN

0041-008X

e-ISSN

—

Volume of the periodical

310

Issue of the periodical within the volume

November

Country of publishing house

US - UNITED STATES

Number of pages

14

Pages from-to

215-228

UT code for WoS article

000386745900022

EID of the result in the Scopus database

2-s2.0-84991503079