ArticleOncotarget2015
Trametinib modulates cancer multidrug resistance by targeting ABCB1 transporter.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 67 citations in OpenAlex.
- ML210 Antagonizes ABCB1- Not ABCG2-Mediated Multidrug Resistance in Colorectal Cancer.Biomedicines · 2025Article
- Evaluation of ABT-751, a novel anti-mitotic agent able to overcome multi-drug resistance, in melanoma cells.Cancer chemotherapy and pharmacology · 2024Article
- MEK-inhibitors decrease Nfix in muscular dystrophy but induce unexpected calcifications, partially rescued with Cyanidin diet.iScience · 2024Article
- Enhancing efficacy of the MEK inhibitor trametinib with paclitaxel inTherapeutic advances in medical oncology · 2024Article
- Vincristine Enhances the Efficacy of MEK Inhibitors in Preclinical Models of KRAS-mutant Colorectal Cancer.Molecular cancer therapeutics · 2023Article
- Article
- Transdermal Delivery of Chemotherapeutics: Strategies, Requirements, and Opportunities.Pharmaceutics · 2021Review
- MiR-873-5p: A Potential Molecular Marker for Cancer Diagnosis and Prognosis.Frontiers in oncology · 2021Review
- EGFR Blockade Reverses Cisplatin Resistance in Human Epithelial Ovarian Cancer Cells.Iranian biomedical journal · 2020Article
- Recombinant Dual-target MDM2/MDMX Inhibitor Reverses Doxorubicin Resistance through Activation of the TAB1/TAK1/p38 MAPK Pathway in Wild-type p53 Multidrug-resistant Breast Cancer Cells.Journal of Cancer · 2020Article
- Single-nucleotide polymorphisms in a short basic motif in the ABC transporter ABCG2 disable its trafficking out of endoplasmic reticulum and reduce cell resistance to anticancer drugs.The Journal of biological chemistry · 2019Article
- MEK inhibition enhances the response to tyrosine kinase inhibitors in acute myeloid leukemia.Scientific reports · 2019Article
- Models used to screen for the treatment of multidrug resistant cancer facilitated by transporter-based efflux.Journal of cancer research and clinical oncology · 2019Review
- WYE-354 restores Adriamycin sensitivity in multidrug-resistant acute myeloid leukemia cell lines.Oncology reports · 2019Article
- Small-molecule inhibition of prostaglandin E receptor 2 impairs cyclooxygenase-associated malignant glioma growth.British journal of pharmacology · 2019Article
- Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts Formation.International journal of molecular sciences · 2019Article
- Interaction between phytotherapy and oral anticancer agents: prospective study and literature review.Medical oncology (Northwood, London, England) · 2019Review
- Clinical Pharmacokinetics and Pharmacodynamics of Dabrafenib.Clinical pharmacokinetics · 2019Review
- Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer.Frontiers in oncology · 2019Article
- Targeting TF-AKT/ERK-EGFR Pathway Suppresses the Growth of Hepatocellular Carcinoma.Frontiers in oncology · 2019Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Overexpression of adenine triphosphate (ATP)-binding cassette (ABC) transporters is one of the main reasons of multidrug resistance (MDR) in cancer cells. Trametinib, a novel specific small-molecule mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor, is currently used for the treatment of melanoma in clinic. In this study, we investigated the effect of trametinib on MDR mediated by ABC transporters. Trametinib significantly potentiated the effects of two ABCB1 substrates vincristine and doxorubicin on inhibition of growth, arrest of cell cycle and induction of apoptosis in cancer cells overexpressed ABCB1, but not ABCC1 and ABCG2. Furthermore, trametinib did not alter the sensitivity of non-ABCB1 substrate cisplatin. Mechanistically, trametinib potently blocked the drug-efflux activity of ABCB1 to increase the intracellular accumulation of rhodamine 123 and doxorubicin and stimulates the ATPase of ABCB1 without alteration of the expression of ABCB1. Importantly, trametinib remarkably enhanced the effect of vincristine against the xenografts of ABCB1-overexpressing cancer cells in nude mice. The predicted binding mode showed the hydrophobic interactions of trametinib within the large drug binding cavity of ABCB1. Consequently, our findings may have important implications for use of trametinib in combination therapy for cancer treatment.
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