Alpha interferon augments cidofovir's antiviral and antiproliferative activities

Abstract

The antiviral and antiproliferative activities of alpha 2a interferon (IFN-alpha 2a) and cidofovir in human papillomavirus type 16 (HPV-16)-transformed keratinocytes were evaluated. The compounds in combination were more effective than comparable levels of either drug alone. Evaluation of effective drug ratios revealed a synergistic cooperation between IFN-alpha 2a and cidofovir in inhibiting the proliferation of HPV-infected cells.

FIG. 1.

Inhibition of HPV-transformed cell proliferation after 2-week treatments with CDV and/or IFN. Percent inhibitions are relative to control (untreated cultures). 1, mock control; 2, 0.15 μM CDV; 3, 50 U of IFN/ml; 3, 0.15 μM CDV plus 50 U of IFN/ml; 4, 1.20 μM CDV; 5, 0.60 μM CDV plus 50 U of IFN/ml.

FIG. 2.

Effects of combination treatments on E6, E7, retinoblastoma (Rb), and p21 from lysates of cultures untreated or treated with 1.0 μM CDV or 0.50 μM CDV plus 50 U of IFN/ml.

FIG. 3.

Effect of IFN and CDV on transformed-cell cycling. Shown are bar graph representations of cell cycle histograms of d-2C cell integrated red fluorescence following 2 days of mock treatment (A) or treatments of 1 μM CDV (B), 50 U of IFN/ml (C), or 50 U of IFN/ml plus 0.50 μM CDV (D).

FIG. 4.

Graphical representation of the median-effect analysis of combinations of IFN-α2a and CDV. Combinations of concentrations that elicited CIs <1 (≥50 U of IFN/ml plus 0.150 μM CDV) were synergistic in their inhibition of HPV-transformed-cell proliferation.