The expression of multidrug resistance-associated protein (MRP) in pancreatic adenocarcinoma cell lines.
The presence of P-glycoprotein (P-gp) and multiple drug resistance-associated protein (MRP) was examined in four human pancreatic adenocarcinoma cell lines (PANC-1, BxPC-3, AsPC-1, and Capan-1). Cellular accumulation of rhodamine 123 and [3H]vincristine were used to determine functional activity of P-gp and MRP, respectively. None of the cells showed any evidence of P-gp in the rhodamine 123 cellular accumulation assays. In contrast, PANC-1, BxPC-3 and AsPC-1 did display an increased accumulation of [3H]vincristine following treatment with either cyclosporin A or verapamil. Western blot analysis confirmed the expression of MRP, and little, if any, measurable P-gp in the cell lysates. These studies suggest that intrinsic drug resistance in pancreatic duct cancer may be due in part to the presence of MRP.
Miller
D W
DW
Department Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha 68198-6025, USA. dwmiller@unmcvc.unmc.edu
Fontain
M
M
Kolar
C
C
Lawson
T
T
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000493:pharmacokinetics
D018528:ATP-Binding Cassette Transporters; D000972:Antineoplastic Agents, Phytogenic; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D014750:Vincristine