P-Glycoprotein but not Topoisomerase II and Glutathione-S-Transferase-Pi Accounts for Enhanced Intracellular Drug-Resistance in LoVo MDR Human Cell Lines
Restricted accessResearch articleFirst published online June, 1992
P-Glycoprotein but not Topoisomerase II and Glutathione-S-Transferase-Pi Accounts for Enhanced Intracellular Drug-Resistance in LoVo MDR Human Cell Lines
The biochemical bases of the multidrug-resistant (MDR) phenotype were investigated in drug-resistant sublines derived from LoVo human colon carcinoma cell lines by doxorubicin (DOX) and teniposide (VM26) selection. In addition to P-glycoprotein-mediated drug extrusion through the plasma-membrane, LoVo MDR cells display a further drug-resistance mechanism. That is, to achieve equitoxic effects, LoVo MDR sublines require much higher intracellular drug concentrations than those required by LoVo drug-sensitive parent cell line. Involvement of mdr1, topoisomerase Il and glutathione-S-transferase-pi (GST-π) drug-resistance systems in intracellular drug resistance was investigated. Pharmacologic and biochemical data indicated that intracellular drug resistance in LoVo MDR sublines is uniquely consequent to the drug-transporting property of intracytoplasmic membrane-bound P-glycoprotein molecules which compartment drugs in vacuolelike structures.
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