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 II and glutathione-S-transferase-pi (GST-pi) 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 vacuole-like structures.
Division of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano, Italy.
M
M
Boiocchi
L
L
Tumiotto
F
F
Giannini
A
A
Viel
G
G
Biscontin
F
F
Sartor
G
G
Toffoli
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003110:Colonic Neoplasms / Q000235:genetics*; D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D004317:Doxorubicin; D004351:Drug Resistance / Q000235:genetics*; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis*; D013713:Teniposide; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D004317:Doxorubicin; D013713:Teniposide; D005982:Glutathione Transferase; D004250:DNA Topoisomerases, Type II