Circumvention of multi-drug resistance in human kidney and kidney carcinoma in vitro.
This report investigated whether the calmodulin inhibitor, trifluoperazine, can circumvent multi-drug resistance both in primary tissue cultures of human kidney and kidney carcinoma. For detection of inherent multi-drug resistance, the expression of P-glycoprotein was determined by immunofluorescence and immunocytochemistry using the monoclonal antibody C219. For detection of doxorubicin resistance and reversal of this resistance by trifluoperazine, the incorporation of nucleic acid precursor was measured after addition of doxorubicin and trifluoperazine, respectively. Both P-glycoprotein expressing resistant normal and malignant kidney tissue cultures could be modified by trifluoperazine. However, sensitive normal kidney and kidney carcinoma cultures were little affected by trifluoperazine. Thus, circumvention of primary resistance to doxorubicin is not limited to tumor cells. This might have important implications for the use of resistance modifiers in the clinical setting.
Volm
M
M
German Cancer Research Center, Department of Experimental Pathology, Heidelberg.
Pommerenke
E W
EW
Efferth
T
T
Löhrke
H
H
Mattern
J
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism; D004317:Doxorubicin / Q000627:therapeutic use; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D012016:Reference Values; D014268:Trifluoperazine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D014268:Trifluoperazine; D004317:Doxorubicin