TY  - JOUR
A1  - Michaelis, Martin
A1  - Rothweiler, Florian
A1  - Nerreter, Thomas
A1  - Rikxoort, Marijke van
A1  - Zehner, Richard
A1  - Dirks, Wilhelm G.
A1  - Wiese, Michael
A1  - Cinatl, Jindrich
T1  - Association between acquired resistance to PLX4032 (vemurafenib) and ATP-binding cassette transporter expression
T2  - BMC Research Notes
N2  - Background: Various kinase inhibitors are known to be ATP-binding cassette (ABC) transporter substrates and resistance acquisition to kinase inhibitors has been associated to increased ABC transporter expression. Here, we investigated the role of the ABC transporters ABCB1, ABCC1, and ABCG2 during melanoma cell resistance acquisition to the V600-mutant BRAF inhibitors PLX4032 (vemurafenib) and PLX4720. PLX4032 had previously been shown to interfere with ABCB1 and ABCG2. PLX4720 had been demonstrated to interact with ABCB1 but to a lower extent than PLX4032.
Findings: PLX4032 and PLX4720 affected ABCC1- and ABCG2-mediated drug transport in a similar fashion. In a panel of 16 V600E BRAF-mutated melanoma cell lines consisting of four parental cell lines and their sub-lines with acquired resistance to PLX4032, PLX4720, vincristine (cytotoxic ABCB1 and ABCC1 substrate), or mitoxantrone (cytotoxic ABCG2 substrate), we detected enhanced ABC transporter expression in 4/4 cytotoxic ABC transporter substrate-resistant, 3/4 PLX4720-resistant, and 1/4 PLX4032-resistant melanoma cell lines.
Conclusion: PLX4032 has the potential to induce ABC transporter expression but this potential is lower than that of PLX4720 or cytotoxic ABC transporter substrates. Since ABC transporters confer multi-drug resistance, this is of relevance for the design of next-line therapies.
KW  - Vemurafenib
KW  - PLX4032
KW  - PLX4720
KW  - Acquired drug resistance
KW  - Melanoma
KW  - Mitoxantrone
KW  - Vincristine
KW  - ABCB1
KW  - ABCC1
KW  - ABCG2
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/35269
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-352693
SN  - 1756-0500
N1  - Copyright © Michaelis et al.; licensee BioMed Central Ltd. 2014
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
VL  - 7
IS  - Art. 710
SP  - 1
EP  - 7
PB  - BioMed Central
CY  - London
ER  -