BMC Research Notes | |
Association between acquired resistance to PLX4032 (vemurafenib) and ATP-binding cassette transporter expression | |
Jindrich Cinatl6  Michael Wiese1  Wilhelm G Dirks3  Richard Zehner4  Marijke van Rikxoort5  Thomas Nerreter6  Florian Rothweiler6  Martin Michaelis2  | |
[1] Pharmaceutical Institute, University of Bonn, An der Immenburg 4, Bonn 53121, Germany;Current address: Centre for Molecular Processing and School of Biosciences, University of Kent, Canterbury Kent CT2 7NJ, UK;Leibniz-Institute Deutsche Sammlung für Mikroorganismen und Zellkulturen GmbH, Inhoffenstraße 7B, Braunschweig 38124, Germany;Institut für Rechtsmedizin, Klinikum der Goethe-Universität, Kennedyallee 104, Frankfurt am Main 60596, Germany;Current address: Institute of Pharmacology and Toxicology, Biomedical Center (BMZ), University of Bonn, Bonn 53127, Germany;Institut für Medizinische Virologie, Klinikum der Goethe-Universität, Paul Ehrlich-Str. 40, Frankfurt am Main 60596, Germany | |
关键词: ABCG2; ABCC1; ABCB1; Vincristine; Mitoxantrone; Melanoma; Acquired drug resistance; PLX4720; PLX4032; Vemurafenib; | |
Others : 1127296 DOI : 10.1186/1756-0500-7-710 |
|
received in 2014-08-21, accepted in 2014-10-02, 发布年份 2014 | |
【 摘 要 】
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.
【 授权许可】
2014 Michaelis et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150220090556297.pdf | 354KB | download | |
Figure 3. | 109KB | Image | download |
Figure 2. | 85KB | Image | download |
Figure 1. | 89KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
【 参考文献 】
- [1]Bollag G, Tsai J, Zhang J, Zhang C, Ibrahim P, Nolop K, Hirth P: Vemurafenib: the first drug approved for BRAF-mutant cancer. Nat Rev Drug Discov 2012, 11:873-886.
- [2]Bucheit AD, Davies MA: Emerging insights into resistance to BRAF inhibitors in melanoma. Biochem Pharmacol 2014, 87:381-389.
- [3]Hegedus C, Ozvegy-Laczka C, Szakács G, Sarkadi B: Interaction of ABC multidrug transporters with anticancer protein kinase inhibitors: substrates and/or inhibitors? Curr Cancer Drug Targets 2009, 9:252-262.
- [4]Van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev 2009, 35:692-706.
- [5]Force T, Kolaja KL: Cardiotoxicity of kinase inhibitors: the prediction and translation of preclinical models to clinical outcomes. Nat Rev Drug Discov 2011, 10:111-126.
- [6]Hegedus T, Orfi L, Seprodi A, Váradi A, Sarkadi B, Kéri G: Interaction of tyrosine kinase inhibitors with the human multidrug transporter proteins, MDR1 and MRP1. Biochim Biophys Acta 2002, 1587:318-325.
- [7]Shi Z, Peng XX, Kim IW, Shukla S, Si QS, Robey RW, Bates SE, Shen T, Ashby CR Jr, Fu LW, Ambudkar SV, Chen ZS: Erlotinib (Tarceva, OSI-774) antagonizes ATP-binding cassette subfamily B member 1 and ATP-binding cassette subfamily G member 2-mediated drug resistance. Cancer Res 2007, 67:11012-11020.
- [8]Hegedüs C, Ozvegy-Laczka C, Apáti A, Magócsi M, Német K, Orfi L, Kéri G, Katona M, Takáts Z, Váradi A, Szakács G, Sarkadi B: Interaction of nilotinib, dasatinib and bosutinib with ABCB1 and ABCG2: implications for altered anti-cancer effects and pharmacological properties. Br J Pharmacol 2009, 158:1153-1164.
- [9]Hegedüs C, Truta-Feles K, Antalffy G, Várady G, Német K, Ozvegy-Laczka C, Kéri G, Orfi L, Szakács G, Settleman J, Váradi A, Sarkadi B: Interaction of the EGFR inhibitors gefitinib, vandetanib, pelitinib and neratinib with the ABCG2 multidrug transporter: Implications for the emergence and reversal of cancer drug resistance. Biochem Pharmacol 2012, 84:260-267.
- [10]Silverton L, Dean M, Moitra K: Variation and evolution of the ABC transporter genes ABCB1, ABCC1, ABCG2, ABCG5 and ABCG8: implication for pharmacogenetics and disease. Drug Metabol Drug Interact 2011, 26:169-179.
- [11]Tamaki A, Ierano C, Szakacs G, Robey RW, Bates SE: The controversial role of ABC transporters in clinical oncology. Essays Biochem 2011, 50:209-232.
- [12]Ieiri I: Functional significance of genetic polymorphisms in P-glycoprotein (MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2). Drug Metab Pharmacokinet 2012, 27:85-105.
- [13]Burger H, Van Tol H, Brok M, Wiemer EA, De Bruijn EA, Guetens G, De Boeck G, Sparreboom A, Verweij J, Nooter K: Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol Ther 2005, 4:747-752.
- [14]Balabanov S, Gontarewicz A, Keller G, Raddrizzani L, Braig M, Bosotti R, Moll J, Jost E, Barett C, Rohe I, Bokemeyer C, Holyoake TL, Brümmendorf TH: Abcg2 overexpression represents a novel mechanism for acquired resistance to the multi-kinase inhibitor Danusertib in BCR-ABL-positive cells in vitro. PLoS One 2011, 6:e19164.
- [15]Tang C, Schafranek L, Watkins DB, Parker WT, Moore S, Prime JA, White DL, Hughes TP: Tyrosine kinase inhibitor resistance in chronic myeloid leukemia cell lines: investigating resistance pathways. Leuk Lymphoma 2011, 52:2139-2147.
- [16]Tsai J, Lee JT, Wang W, Zhang J, Cho H, Mamo S, Bremer R, Gillette S, Kong J, Haass NK, Sproesser K, Li L, Smalley KS, Fong D, Zhu YL, Marimuthu A, Nguyen H, Lam B, Liu J, Cheung I, Rice J, Suzuki Y, Luu C, Settachatgul C, Shellooe R, Cantwell J, Kim SH, Schlessinger J, Zhang KY, West BL, et al.: Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci U S A 2008, 105:3041-3046.
- [17]Durmus S, Sparidans RW, Wagenaar E, Beijnen JH, Schinkel AH: Oral availability and brain penetration of the B-RAFV600E inhibitor vemurafenib can be enhanced by the P-GLYCOprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar. Mol Pharm 2012, 9:3236-3245.
- [18]Mittapalli RK, Vaidhyanathan S, Sane R, Elmquist WF: Impact of P-glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2) on the brain distribution of a novel B-RAF Inhibitor: Vemurafenib (PLX4032). J Pharmacol Exp Ther 2012, 342:33-40.
- [19]Michaelis M, Rothweiler F, Nerreter T, Van Rikxoort M, Sharifi M, Wiese M, Ghafourian T, Cinatl J Jr: Differential effects of the oncogenic BRAF Inhibitor PLX4032 (vemurafenib) and its progenitor PLX4720 on ABCB1 function. J Pharm Pharm Sci 2014, 17:154-168.
- [20]Wu CP, Sim HM, Huang YH, Liu YC, Hsiao SH, Cheng HW, Li YQ, Ambudkar SV, Hsu SC: Overexpression of ATP-binding cassette transporter ABCG2 as a potential mechanism of acquired resistance to vemurafenib in BRAF(V600E) mutant cancer cells. Biochem Pharmacol 2013, 85:325-334.
- [21]Weber K, Bartsch U, Stocking C, Fehse B: A multicolor panel of novel lentiviral "gene ontology" (LeGO) vectors for functional gene analysis. Mol Ther 2008, 16:698-706.
- [22]Michaelis M, Rothweiler F, Nerreter T, Sharifi M, Ghafourian T, Cinatl J Jr: Karanjin interferes with ABCB1, ABCC1, and ABCG2. J Pharm Pharm Sci 2014, 17:92-105.
- [23]Sterz K, Möllmann L, Jacobs A, Baumert D, Wiese M: Activators of P-glycoprotein: Structure-activity relationships and investigation of their mode of action. ChemMedChem 2009, 4:1897-1911.
- [24]Häcker HG, de la Haye A, Sterz K, Schnakenburg G, Wiese M, Gütschow M: Analogs of a 4-aminothieno[2,3-d]pyrimidine lead (QB13) as modulators of P-glycoprotein substrate specificity. Bioorg Med Chem Lett 2009, 19:6102-6105.
- [25]Chartrain M, Riond J, Stennevin A, Vandenberghe I, Gomes B, Lamant L, Meyer N, Gairin JE, Guilbaud N, Annereau JP: Melanoma chemotherapy leads to the selection of ABCB5-expressing cells. PLoS One 2012, 7:e36762.
- [26]Brózik A, Hegedüs C, Erdei Z, Hegedus T, Özvegy-Laczka C, Szakács G, Sarkadi B: Tyrosine kinase inhibitors as modulators of ATP binding cassette multidrug transporters: substrates, chemosensitizers or inducers of acquired multidrug resistance? Expert Opin Drug Metab Toxicol 2011, 7:623-642.
- [27]Chaudhary PM, Roninson IB: Induction of multidrug resistance in human cells by transient exposure to different chemotherapeutic drugs. J Natl Cancer Inst 1993, 85:632-639.
- [28]Sukhai M, Piquette-Miller M: Regulation of the multidrug resistance genes by stress signals. J Pharm Pharm Sci 2000, 3:268-280.
- [29]Cressman AM, Petrovic V, Piquette-Miller M: Inflammation-mediated changes in drug transporter expression/activity: implications for therapeutic drug response. Expert Rev Clin Pharmacol 2012, 5:69-89.