Combretastatin A4 phosphate induces rapid regression of tumor neovessels and growth through interference with vascular endothelial-cadherin signaling
J. Clin. Invest. Loïc Vincent, et al. 115:2992 doi:10.1172/JCI24586 [Go to this article.]

Figure 1
CA4P inhibits growth factor–induced endothelial cell proliferation and migration. (A) CA4P inhibits HUVEC proliferation. HUVECs were incubated with or without growth factors, and CA4P was added at different concentrations. Cells were then counted at the indicated time points. Results of 4 experiments in duplicate are expressed as the mean number of cells ± SEM (*P < 0.05, **P < 0.01, ^#P < 0.001 compared with CA4P-untreated cells; n = 4). (B) SMCs are not sensitive to CA4P. HUVECs or SMCs were incubated with CA4P, and cells were counted after 48 hours. Results of 4 experiments in duplicate are expressed as the mean number of cells ± SEM (**P < 0.01, ^#P < 0.001 compared with CA4P-untreated cells; n = 4). (C) HUVECs are resistant to CA4P when cocultured with SMCs. HUVECs and SMCs were seeded together, incubated with CA4P, and counted after 48 hours. Results of 4 experiments in duplicate are expressed as the mean number of cells ± SEM. (D) CA4P inhibits HUVEC migration. A lesion was produced across the HUVECs’ monolayers, and unstimulated or FGF-2–stimulated cell monolayers were incubated with CA4P for 24 hours and then photographed. A representative picture is shown. Magnification: ×4. Scale bar, 500 μm. (E) Quantification of recovery of each denuded area after CA4P treatment. Results are expressed as the ratio of the number of invading cells to the number of migrating cells in absence of CA4P ± SEM (^#P < 0.001 compared with CA4P-untreated cells; ^†P < 0.001 compared with FGF-2–stimulated endothelial cells; n = 5).