Tags

Type your tag names separated by a space and hit enter

Association between acquired resistance to PLX4032 (vemurafenib) and ATP-binding cassette transporter expression.
BMC Res Notes. 2014 Oct 10; 7:710.BR

Abstract

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.

Authors+Show Affiliations

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableInstitut für Medizinische Virologie, Klinikum der Goethe-Universität, Paul Ehrlich-Str, 40, Frankfurt am Main 60596, Germany. Cinatl@em.uni-frankfurt.de.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25300205

Citation

Michaelis, Martin, et al. "Association Between Acquired Resistance to PLX4032 (vemurafenib) and ATP-binding Cassette Transporter Expression." BMC Research Notes, vol. 7, 2014, p. 710.
Michaelis M, Rothweiler F, Nerreter T, et al. Association between acquired resistance to PLX4032 (vemurafenib) and ATP-binding cassette transporter expression. BMC Res Notes. 2014;7:710.
Michaelis, M., Rothweiler, F., Nerreter, T., van Rikxoort, M., Zehner, R., Dirks, W. G., Wiese, M., & Cinatl, J. (2014). Association between acquired resistance to PLX4032 (vemurafenib) and ATP-binding cassette transporter expression. BMC Research Notes, 7, 710. https://doi.org/10.1186/1756-0500-7-710
Michaelis M, et al. Association Between Acquired Resistance to PLX4032 (vemurafenib) and ATP-binding Cassette Transporter Expression. BMC Res Notes. 2014 Oct 10;7:710. PubMed PMID: 25300205.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association between acquired resistance to PLX4032 (vemurafenib) and ATP-binding cassette transporter expression. AU - Michaelis,Martin, AU - Rothweiler,Florian, AU - Nerreter,Thomas, AU - van Rikxoort,Marijke, AU - Zehner,Richard, AU - Dirks,Wilhelm G, AU - Wiese,Michael, AU - Cinatl,Jindrich,Jr Y1 - 2014/10/10/ PY - 2014/08/21/received PY - 2014/10/02/accepted PY - 2014/10/11/entrez PY - 2014/10/11/pubmed PY - 2015/6/11/medline SP - 710 EP - 710 JF - BMC research notes JO - BMC Res Notes VL - 7 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. SN - 1756-0500 UR - https://www.unboundmedicine.com/medline/citation/25300205/Association_between_acquired_resistance_to_PLX4032__vemurafenib__and_ATP_binding_cassette_transporter_expression_ L2 - https://bmcresnotes.biomedcentral.com/articles/10.1186/1756-0500-7-710 DB - PRIME DP - Unbound Medicine ER -