Targeting mTOR and Src restricts hepatocellular carcinoma growth in a novel murine liver cancer model
Fig 4
Limiting mTOR and Src activity restricts HCC growth.
A, A52 subcutaneous tumor growth curves when treated with Rapamycin (Rapa; n = 8) and versus placebo (n = 6). Linear regression demonstrated that Rapamycin (p <0.0001) significantly reduced tumour growth. B-C, Western blotting showed a significant increase in p-Src/Src in the Rapamycin treated group (*p<0.05). D, Dose-dependent signaling analyses showed that Rapamycin (0–300 nM) reduced 4E-BP1 and p70S6K phosphorylation and Dasatinib (0–300 nM) reduced Src phosphorylation. The combination of Rapamycin and Dasatinib reduced 4E-BP1, p70S6K, Src and AKT phosphorylation. ß-actin loading control. E, Growth curves of 500 mm3 subcutaneous tumors treated with Dasatinib, Rapamycin, or Rapamycin + Dasatinib (n = 8, all groups). Linear regression analyses showed that Dasatinib or Rapamycin had no effect on tumor growth kinetics. The combination of Rapamycin + Dasatinib reduced tumor growth kinetics (p = 0.0012). F, Fold change in tumor volume per tumor for the treatment period Day 0–15 was determined by one-way ANOVA and Bonferroni’s multiple comparisons test. Versus placebo, Dasatinib or Rapamycin had no effect, and Rapamycin + Dasatinib significantly increased the fold-reduction in tumor volume (p = 0.029).