Abstract
Sorafenib and sunitinib is a small molecule inhibitor of certain receptor tyrosine kinases, and have improved outcomes for patients with advanced renal cell carcinoma. Inhibitory concentration of 50% cell growth of sorafenib significantly rose to 6.4-fold in a multidrug resistance protein 2 (MRP2) transfected cell line versus control cell line. The concentration of sorafenib was significantly decreased to 74% of control cells after 3 h treatment. In contrast, a tyrosine kinase inhibitor sunitinib did not show alteration of inhibitory concentration of 50% cell growth and accumulation into the cells of MRP2 transfected cells. The present study suggest that sorafenib is a substrate for MRP2, suggesting that MRP2 may implicate drug resistance to sorafenib.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily B / metabolism*
-
ATP-Binding Cassette Sub-Family B Member 4
-
Animals
-
Antineoplastic Agents / metabolism*
-
Antineoplastic Agents / pharmacology
-
Benzenesulfonates / metabolism*
-
Benzenesulfonates / pharmacology
-
Carcinoma, Renal Cell / metabolism
-
Cell Cycle / drug effects
-
Cell Line, Tumor
-
Cell Survival / drug effects
-
Drug Resistance, Neoplasm*
-
Humans
-
Indoles / metabolism*
-
Indoles / pharmacology
-
Kidney Neoplasms / metabolism
-
Niacinamide / analogs & derivatives
-
Phenylurea Compounds
-
Protein Kinase Inhibitors / metabolism*
-
Protein Kinase Inhibitors / pharmacology
-
Protein-Tyrosine Kinases / antagonists & inhibitors
-
Pyridines / metabolism*
-
Pyridines / pharmacology
-
Pyrroles / metabolism*
-
Pyrroles / pharmacology
-
Sorafenib
-
Substrate Specificity
-
Sunitinib
-
Swine
-
Transfection
Substances
-
ATP Binding Cassette Transporter, Subfamily B
-
Antineoplastic Agents
-
Benzenesulfonates
-
Indoles
-
Phenylurea Compounds
-
Protein Kinase Inhibitors
-
Pyridines
-
Pyrroles
-
Niacinamide
-
Sorafenib
-
Protein-Tyrosine Kinases
-
Sunitinib