Modulation of P-glycoprotein-mediated multidrug resistance by monoclonal antibodies, immunotoxins or antisense oligodeoxynucleotides in kidney carcinoma and normal kidney cells.
In the present investigation we show that both monoclonal antibodies against P-170 (265/F4, MRK 16, and HYB 612) and 265/F4-ricin alpha-chain immunotoxin are useful tools for the eradication of kidney carcinoma and normal kidney primary cell cultures with high P-170 expression, whereas kidney tumor and normal kidney cell lines with low amounts of P-170 are less affected. Furthermore, we found that the expression of P-170 in both kidney tumor and normal kidney cell cultures with high amounts of P-170 was inhibited by antisense oligodeoxynucleotides complementary to base pairs -9 to +6 of the MDR1 gene. These data indicate that these approaches for the eradication of P-170 expressing multidrug-resistant cells are not limited to tumors but also affect P-170 expressing normal cells.
Efferth
T
T
German Cancer Research Centre, Heidelberg.
Volm
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001483:Base Sequence; D002352:Carrier Proteins / Q000276:immunology / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D004351:Drug Resistance; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D000922:Immunotoxins; D008562:Membrane Glycoproteins; D016376:Oligonucleotides, Antisense