Trabectedin (ET-743, Yondelis) is a substrate for P-glycoprotein, but only high expression of P-glycoprotein confers the multidrug resistance phenotype
| Autor: | Jan-Hendrik Beumer, Luis Lopez-Lazaro, Niels E. F. Franke, Tessa Buckle, Mariët Ouwehand, Olaf van Tellingen, Jos H. Beijnen, Jan H.M. Schellens |
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| Rok vydání: | 2006 |
| Předmět: |
Intracellular Fluid
Cell Membrane Permeability Paclitaxel Cell Survival Swine ATP-binding cassette transporter Drug resistance Dibenzocycloheptenes Dioxoles Pharmacology Transfection Cell Line chemistry.chemical_compound Inhibitory Concentration 50 Mice Tetrahydroisoquinolines medicine Cytotoxic T cell Animals Humans Pharmacology (medical) ATP Binding Cassette Transporter Subfamily B Member 1 Carbon Radioisotopes Antineoplastic Agents Alkylating Trabectedin P-glycoprotein biology urogenital system Membrane Transport Proteins Biological Transport Drug Resistance Multiple Oncology chemistry Cell culture Drug Resistance Neoplasm biology.protein Cancer research Quinolines LLC-PK1 Cells medicine.drug |
| Zdroj: | Investigational new drugs. 25(1) |
| ISSN: | 0167-6997 |
| Popis: | Trabectedin (ET-743, Yondelis™) is a novel anticancer drug currently undergoing phase II and III investigations. There are various and conflicting reports whether trabectedin is a substrate for P-glycoprotein (P-gp), an important factor in drug disposition and multi-drug resistance (MDR). We have now unambiguously shown that trabectedin is a P-gp substrate by investigating vectorial transport over monolayers of LLC-PK1 pig kidney and Madine-Darby Canine kidney (MDCK) cells and the mdr1a and/or MDR1 transfected subclones. We further characterized the cytotoxic effects and cellular accumulation of trabectedin in these cell lines as well as in a panel of other cell lines with high or moderate expression levels of P-gp. Trabectedin displayed the typical MDR phenotype only in highly P-gp expressing cell lines, but not in cell lines with expression levels more closely conforming to clinical samples, suggesting that P-gp will not confer resistance to trabectedin in cancer patients. |
| Databáze: | OpenAIRE |
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