Fig. 4
The effect of gefitinib-FTY720 combination therapy on TNBC xenograft tumor growth in nude mice. a Mean increases ± SEM (n = 5) in tumor volume from the commencement of treatment, 28 days after MDA-MB-468 cell implantation (tumor size ~100 mm3). All mice were sacrificed on day 25, the day the largest tumor reached 500 mm3 (Protocol 1). Gefitinib: 50 mg/kg; FTY720: 3 mg/kg. There is a significant effect of treatment overall (P = 0.044, repeated measures ANOVA). At sacrifice the increase in control-treated tumors was threefold greater than that of combination-treated tumors (*, P = 0.041, one-way ANOVA) but not significantly different from either monotherapy. b Kaplan-Meier analysis for survival effect of combination treatment, compared to control treatment and either monotherapy: log-rank P = 0.018. Treatment (gefitinib, 25 or 50 mg/kg; FTY720, 5 mg/kg) in groups of five mice commenced 28 days after MDA-MB-468 cell implantation (tumor size ~100 mm3) and each mouse was sacrificed when its tumor reached 500 mm3 (Protocol 2). Data are combined for gefitinib at 25 or 50 mg/kg. c For HCC1806 cell tumors, treatment (gefitinib, 25 mg/kg; FTY720, 5 mg/kg) commenced 7 days after cell implantation, (tumor size ~200 mm3). Each mouse was sacrificed when its tumor reached 1000 mm3; mean increases ± SEM (n = 10) in tumor volume are shown for time points until the first mouse in each group was culled. Overall effect of treatment: P = 0.002, repeated measures ANOVA. The increase in combination-treated tumors is significantly less than controls (* P = 0.010), gefitinib-treated (P = 0.006), and FTY720-treated (P = 0.026) tumors (post hoc Tukey’s test). d Kaplan-Meier analysis from the experiment described in Fig. 2c. Survival effect of combination treatment compared to control-treated mice and those on either monotherapy: log-rank P = 0.001. e For HCC70 cell tumors, treatment (gefitinib, 25 mg/kg; FTY720, 5 mg/kg) in groups of ten mice commenced when tumor size was ~100 mm3 (about 14 days after implantation). Kaplan-Meier analysis for survival effect of combination treatment, compared to control mice and those on either monotherapy: log-rank P = 0.218