Interferon alpha 2b differentially affects proliferation of two human renal cell carcinoma cell lines differing in the P-glycoprotein-associated multidrug-resistant phenotype

Purpose: Interferon alpha (IFN alpha) has been used in the immunotherapy of renal cell carcinoma (RCC), but the various mechanisms of its antiprolifer ative effects are poorly understood. Recent evidence suggests that IFN alph a is involved in the up-regulation of multidrug resistance (MDR) gene expre ssion, and that the MDR gene product, P-glycoprotein (Pgp), facilitates the transport of several cytokines, some of which have been implicated in medi ating tumor antiproliferative effects. We hypothesized that IFN alpha-induc ed antiproliferative activity may require Pgp-mediated transport, and that susceptibility to IFN alpha may thus correlate with Pgp expression. Methods : Pgp expression by the human RCC cell lines KTCTL-2 and KTCTL-26 was chara cterized by immunofluorescence staining, using the Pgp-specific primary ant ibodies C219 and JSB1. KTCTL-2 and KTCTL-26 cell lines were subsequently tr eated with IFN alpha 2b, and growth kinetics of treated and control cell cu ltures were determined daily by cell counting. Results: KTCTL-2 expresses P gp at low levels, whereas KTCTL-26 is a highly expressing cell line. IFNa2b treatment abrogated cell proliferation in KTCTL-26, whereas proliferation of KTCTL-2 was only partially inhibited. Conclusions: We have identified tw o RCC cell lines that differ in the MDR phenotype and exhibit different res ponses to the antiproliferative activity of IFN alpha 2b. These preliminary findings raise the possibility that susceptibility to the antiproliferativ e effects of IFN alpha 2b may correlate with Pgp expression, and further st udies are warranted.