Analyses of tissues after drug treatment.

A, Histology for phospho-histone H3 (P3H3; n = 4–6 for each group) showed that the Dasatinib (Dasat), Rapamycin (Rapa) and Rapamycin + Dasatinib treatments successively reduced tumor cell proliferation and increased apoptosis. Proliferation: control versus Dasatinib (p = 0.01); Placebo versus Rapamycin (p = 0.0001); control versus Rapamycin + Dasatinib, (p = 0.0001); Dasatinib versus Rapamycin (p = 0.05); Dasatinib versus Rapamycin + Dasatinib (p = 0.0001) and Rapamycin versus Rapamycin + Dasatinib (p = 0.05). B, Histology by TUNEL (n = 4–6 for each group) showed that compared to control, only Rapamycin + Dasatinib treatment increased tumor cell apoptosis (p = 0.0001), was significantly greater than that observed for Dasatinib (p = 0.0001) and Rapamycin (p = 0.01) treatments. C-D, Representative western blot densitometry analyses showing that compared to control, a small but significant reduction in p-mTOR/mTOR density in all groups (p = 0.05); an increase in p-4E-BP1/4E-BP1 for Rapamycin (p = 0.05) and no significant change in Dasatinib or Rapamycin + Dasatinib; reduced p-p70S6K/p70S6K density for all groups (p = 0.05 for Rapamycin or Dasatinib, and p = 0.01 for Rapamycin + Dasatinib); and reduced p-Src/Src and p-AKT/AKT for control versus Rapamycin + Dasatinib only (p = 0.05). E, Tumor pathology was necrotic in the Rapamycin + Dasatinib treatment group.