Fig. 1.

S-222611 inhibits the growth of NCI-N87 tumor and phosphorylation of epidermal growth factor receptor (EGFR) and human epidermal growth factor 2 (HER2) in the tumor. The animal model was prepared by subcutaneous implantation of human gastric cancer cells, NCI-N87 into the back of nude mice. (a) After randomization at 3 days after implantation (n = 9), vehicle or multiple doses of S-222611 or lapatinib were orally administered daily for 21 days. To avoid visual complexity, only two doses of lapatinib are depicted in this graph. The four full doses of lapatinib are presented in Figure S1. Tumor volume was measured twice or thrice weekly and the mean tumor volume with SD was represented at each data point. **P < 0.01 (versus vehicle, Dunnett's test). (b–e) After randomization at 12 days after implantation (n = 5), vehicle or multiple doses of S-222611 or lapatinib were administered orally. The relative phosphorylations of EGFR (b,d) and HER2 (c,e) were calculated and the mean with SD is presented in each bar graph. In b and c, the relative phosphorylations of EGFR (b) and HER2 (c) in tumor collected 24 h after administration of the indicated doses of S-222611 or lapatinib are shown. In d and e, the relative phosphorylation levels of EGFR (d) and HER2 (e) in the tumor collected 6 and 24 h after administration of 50 mg/kg of S-222611 or lapatinib are shown. ns: P ≥ 0.05, **: P < 0.01 (Tukey's multiple comparison). (f) The fold increase of the IC₅₀ of each short-time pulse treatment compared to that of 72-h treatment was calculated and the mean with SD is presented in each bar graph (n = 3).