Figure 5

Notch Modulates Akt Activation and Cooperates with mTOR Inhibitor in Tumor Proliferation. (A) Akt inactivation and PTEN phosphorylation by Rapamycin (10 μM) are enhanced when MRK003 (10 μM) is added. MRK003 also enhances induction of pro-apoptic Fox3a and Bim by the mTOR inhibitor rapamycin. (B) Notch inhibition results in higher expression of RhoA, and the induction of RhoA is enhanced when rapamycin was combined with MRK003. No change is observed with Rock1. (C, D) In the MTT survival assays, the combination of MRK003 and rapamycin also leads to higher tumor cytoxicity in vitro, compared to either agents alone, in both murine K399 and human Panc-1 pancreas cancer cell lines.