Figure 9

Combined targeting of mTOR and c-MET results in superior antitumor effects on EpS tumor growth in vivo . A) Effects of combination therapy with RAD001 and INC280 on EpS xenograft tumor growth. Mice bearing Asra-EPS and VAESBJ xenograft tumors were treated with INC280 (n = 7), RAD001 (n = 7), their combination (n = 7), or vehicle control (n = 8). In the INC280 and combination groups, mice were treated with 10 mg/kg INC280 once a day. In the RAD001 and combination groups, mice were treated with 5 mg/kg RAD001 thrice a week. Points, mean; bars, SD. *, p < 0.05, **, p < 0.01, compared with control treatment; #, p < 0.05, compared with INC280 or RAD001 monotherapy. B) Asra-EPS and VAESBJ xenograft tumor weight in the four groups. The average Asra-EPS tumor weights recorded at termination of the study were: control group, 1106 ± 600 mg; INC280 group, 188 ± 113 mg; RAD001 group, 210 ± 93 mg; and combination group, 57 ± 40 mg. The average VAESBJ tumor weights were: control group, 1337 ± 376 mg; INC280 group, 818 ± 311 mg; RAD001 group, 718 ± 195 mg; and combination group, 302 ± 77 mg. Columns, mean; bars, SD. *, p < 0.05, **, p < 0.01, compared with control treatment; #, p < 0.05, compared with INC280 or RAD001 monotherapy. C) Appearance of the resected Asra-EPS and VAESBJ xenograft tumors in the four groups. D) Body weight of mice bearing Asra-EPS xenograft tumors in the four groups. Points, mean; bars, SD. E) Effects of combined therapy with RAD001 and INC280 on phosphorylation of S6RP and c-MET in Asra-EPS and VAESBJ xenograft tumors. Xenograft tumors were harvested 3 hours after the last administration and then cell lysates were prepared.