Interferon α2b differentially affects proliferation of two human renal cell carcinoma cell lines differing in the P-glycoprotein-associated multidrug-resistant phenotype

Abstract

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.

Investigation of multidrug resistance in cultured human renal cell carcinoma cells by 31P-NMR spectroscopy and treatment survival assays

“…At a dose of 10000 U/ml there was no effect on KTCTL-26 cells while KTCTL-2 exhibited a minor growth enhancement similar to that observed previously [32] for a 48 h incubation (ca. 112% survival).…”

“…112% at 48 h, 55% at 96 h after treatment) for KTCTL-2 cells. The KTCTL-26 cell line was more sensitive to IFN-α2b; cell survival was only about 59% at 48 h and 28% at 96 h after treatment [32]. For comparison, in the current study with 40 h incubations, IFN-α2b at 10000 U/ml resulted in 113 ± 13% survival for KTCTL-2 and 99 ± 3% for KTCTL-26 (group 1H, Table 2).…”

“…2b and 2c with 0-1.1 µM VBL and 0-10 µM DIL in the presence of 2000 U/ml IFN-α2b (groups 1D-1G, Table 2), i.e. at a more clinically relevant IFN-α dose than the 10000 U/ml used previously [32]. As expected, treatment with 2000 U/ml IFN-α2b alone had little effect on KTCTL-2 survival (93.7 ± 4.6% vs. untreated controls, Fig.…”

“…Immediately prior to use, vials were removed from the refrigerator, and solutions were prepared according to the manufacturer's instructions, with serial dilutions to obtain the desired concentrations in culture medium. Recombinant interferon (IFN)-α2b (Intron A, Essex Pharma, Munich, FRG) was used as previously described [32].…”

Astroglial expression of the P-glycoprotein is controlled by intracellular CNTF

“…This involved, in particular, several agents that had also been shown to stimulate P-gp expression in other cell types, such as Interferon-α and -γ (IFN-α, γ) [20-22], Tumor Necrosis Factor alpha (TNF-α) [21,23] and dibutyryl-cyclic-AMP [24], and also a number of other compounds classically used to induce astroglial differentiation in vitro . Surprisingly, only a few of these factors drove astroglial P-gp expression, indicating that P-gp overexpression is not just related to astroglial differentiation, but appears as a specific response to certain stimuli.…”