Fig. 5.

The effect of gefitinib-FTY720 therapy on syngeneic 4T1 mammary tumor growth in immune-deficient and -competent mice. a Gefitinib and FTY720 synergistically inhibit cell proliferation of 4T1 murine mammary carcinoma cells, measured by IncuCyte real-time imaging. Data are expressed as the increase in percent confluence, corrected for confluence at time zero, and are mean values ± SD at each time point for triplicate wells for each treatment. Treatments are: control (blue), gefitinib 3 μM (red), FTY720 1 μM (orange), and both drugs combined (green). CI = combination index. b Growth of 4T1 murine mammary tumors in untreated nude (immune-deficient) and wild-type (immune-competent) BALB/c mice. In both strains tumors took a mean of 24 ± 3 days after implantation to reach at least 1000 mm³. c In nude mice, single or combination therapy had no significant effect on tumor growth rate. Red squares: control; blue circles: gefitinib, 50 mg/kg; green triangles: FTY720, 5 mg/kg; orange diamonds: combination. d Kaplan-Meier survival analysis showed that gefitinib-FTY720 combination therapy did not significantly extend survival compared to mono- or no therapy (log-rank P = 0.058). e In wild-type mice, combination therapy, but neither monotherapy, significantly decreased tumor growth rate compared to no therapy (P = 0.041, Tukey’s post hoc test after repeated measures ANOVA). f Combination therapy significantly extended survival (log-rank P = 0.001) compared to mice receiving mono- or no therapy