Angiogenic factors (bFGF and VEGF, etc) inhibited SDRT-induced EC apoptosis, although the underlying mechanism remains unclear [13, 14]. In order to demonstrate that the synergistic effect of Pazopanib results from inhibition of VEGF signaling we tested these effects on BAEC in vitro, which has been demonstrated to be an ideal model for radiosensitization to SDRT . As shown in Figure 5A, 100 ng/ml VEGF elicited a rapid activation of VEGFR2 and 2 crucial downstream proteins, ERK and Akt in BAECs. Pazopanib at a low concentration (10 ng/ml) did not repress VEGF-induced phosphorylation of VEGFR2, Akt and Erk, whereas high concentration of Pazopanib (>100 ng/ml) showed a dramatic inhibition effect of all three, and 500 ng/ml Pazopanib led to a complete repression of phosphorylation of these targets. These results indicated that Pazopanib is a potent inhibitor of VEGF signaling in BAECs. Next, we assessed whether Pazopanib administration could induce BAEC apoptosis. Similar to our results with DC101 (antibody against VEGF - R2) , Pazopanib administration showed the best induction of apoptosis in BAEC at 24 h (Figure 5B). Based on these results we pre-incubated the cells with Pazopanib for 16 h and examined a dose response radiosensitization in BAECs. As shown in Figure 5C, a massive increase in BAEC apoptosis (15.8% ± 1.5% at 5 Gy and 28.9% ± 2.2% at 10 Gy) was achieved at 8 h post SDRT, whereas Pazopanib alone (100 ng/ml) induced a very minimal apoptotic effect. Importantly, substantially enhanced EC apoptosis (22.9% ± 2.5% at 5 Gy and 40.8% ± 1.9% at 10 Gy) was generated in the combined condition (Figure 5C), which was significantly higher than with each treatment alone. These results provided strong evidence that Pazopanib has a direct effect on the endothelial cells and synergizes with SDRT in their dysfunction.