The relative activities of
interferon-alpha2b (IFN-alpha2b) and
polyethylene glycol(12000)-IFN-alpha2b (PEG-IFN-alpha2b) were assessed in cell culture studies using WM9
melanoma or ACHN
renal cell carcinoma cell lines.
Interferon-alpha2b and PEG-IFN-alpha2b had identical antiproliferative activities when tested in cell proliferation studies conducted with equivalent
antiviral units of each IFN preparation. Neither IFN formulation was effective in inducing apoptosis in WM9
melanoma cells, but both increased slightly the percentage of ACHN cells undergoing apoptosis as assessed by
Annexin V staining.
Interferon-alpha2b and PEG-IFN-alpha2b both activated signal transducer and activator of transcription complexes, and the duration of complex activation was similar for both IFN formulations. Induction of different IFN-stimulated genes was assessed by Northern blotting and the quantitative real-time reverse transcription-coupled polymerase chain reaction (RT-PCR) in WM9
melanoma, ACHN
renal cell carcinoma, U937
lymphoma, and MOLT-4 and Mono Mac 6
leukemia cell lines.
Interferon-alpha2b and PEG-IFN-alpha2b had equivalent gene-modulatory activities within each of these tumor cell lines, although cell line-specific induction patterns were observed. When compared with the
antiviral 50% inhibitory concentration (IC(50)) values, the dose-dependent gene expression data correlated with cell sensitivity to IFN treatment. Together, the
drug comparability and cell sensitivity data suggest a predictive relation between dose, time,
antiviral activity, and gene transcription effects. Therefore, although the specific activity of
IFN-alpha2b is approximately three times greater than PEG-IFN-alpha2b, the two preparations have identical in vitro
biologic activities when applied to cells at equivalent
antiviral units.