Interferon alpha2b differentially affects proliferation of two human renal cell carcinoma cell lines differing in the P-glycoprotein-associated multidrug-resistant phenotype.
OBJECTIVE
Interferon alpha (IFNalpha) has been used in the immunotherapy of renal cell carcinoma (RCC), but the various mechanisms of its antiproliferative effects are poorly understood. Recent evidence suggests that IFNalpha is involved in the up-regulation of multidrug resistance (MDR) gene expression, and that the MDR gene product, P-glycoprotein (Pgp). facilitates the transport of several cytokines, some of which have been implicated in mediating tumor antiproliferative effects. We hypothesized that IFNalpha-induced antiproliferative activity may require Pgp-mediated transport, and that susceptibility to IFNalpha may thus correlate with Pgp expression.


METHODS
Pgp expression by the human RCC cell lines KTCTL-2 and KTCTL-26 was characterized by immunofluorescence staining, using the Pgp-specific primary antibodies C219 and JSB1. KTCTL-2 and KTCTL-26 cell lines were subsequently treated with IFNalpha2b, and growth kinetics of treated and control cell cultures were determined daily by cell counting.


RESULTS
KTCTL-2 expresses Pgp at low levels, whereas KTCTL-26 is a highly expressing cell line. IFNalpha2b treatment abrogated cell proliferation in KTCTL-26, whereas proliferation of KTCTL-2 was only partially inhibited.


CONCLUSIONS
We have identified two RCC cell lines that differ in the MDR phenotype and exhibit different responses to the antiproliferative activity of IFNalpha2b. These preliminary findings raise the possibility that susceptibility to the antiproliferative effects of IFNalpha2b may correlate with Pgp expression, and further studies are warranted.
Frank
M H
MH
Department of Urology, University of Heidelberg, Germany. mhfrank@bics.bwh.harvard.edu
Pomer
S
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010641:Phenotype; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins