Figure 3
Saracatinib combined with lapatinib induces a cooperative antitumor effect in JIMT-1 tumor xenografts. (A) Seven days after orthotopic injection of JIMT-1 cells, mice were randomized (10/group) to receive lapatinib, saracatinib, or both (see Materials and methods section for details). The control group is constituted of animals treated with DMSO vehicle. The one-way ANOVA test was used to compare tumor sizes among treatment groups at the median survival of the control group (32.5 days). Tumors were significantly smaller in animals administered the combination than in mice treated with a single agent (P < 0.1 × 10-2). (B) Median survival was significantly longer in animals injected with the combination versus control animals (P < 0.1 × 10-2) and saracatinib-treated animals (P < 0.5 × 10-2), evaluated by log-rank test. (C) Experimental metastasis assay. Percentage of human Alu sequences in the lungs of mice after tail-vein injection with JIMT-1 cells and treatment with lapatinib, saracatinib, or both (see Materials and methods section for details). Data are calculated by using mean cycle-threshold values. (D) Western blot analysis of total lysates from JIMT-1 tumor specimens of two mice killed on day 25. Tumors derived from each treatment group were pooled during lysis to obtain a single specimen. The relative optical density of phosphoprotein levels normalized to the actin level is shown.