Figure 3: Vasculature as a drug target.
From: 3D microtumors in vitro supported by perfused vascular networks
(a,b) Effect of Pazopanib on vascular network integrity. VMOs were exposed to drug from day 4 to 6. Data are normalized to day of first drug exposure and are shown as percentage of control. Error bars show mean ± s.d (n = 3) (p < 0.05 vs control). (c–e) Effect of the anti-vascular agents, Sorafenib (1 μM) and Vincristine (10 nM) on total vessel length and total number of branch points in the VMO. VMOs were exposed to the drug between days 5 to 7 and cultured for an additional 96 h. Error bars show mean ± s.d (n = 3) (p < 0.05 vs control). Sorafenib induces vessel regression (c), whereas vincristine induces vascular damage (d). (f) Effect of 10 different RTK inhibitors on vascular network integrity. VMOs were exposed to drugs between days 5 and 7 and cultured for an additional 96 h. Data are normalized to first day of drug exposure and are shown as percentage of control. Error bars show mean ± s.d (n = 3- 5) (*p < 0.05 vs control; **p < 0.001; γp < 0.05 vs Apatinib alone). (g) Anti-cancer drugs that target tumor, vasculature, or both. HCT116 tumor cells in a VMT exposed to Pazopanib (1 μM), Oxaliplatin (5 μM) and Vincristine (10 nM). Images before and after drug exposure are of the same VMT (Scale bar 100 μm). (h) Summary of the relative IC50tumor/IC50vessel values (from (g) and data not shown) plotted on a log scale. Drugs extending to the right are more effective, relatively, on vessels, whereas those on the left are more effective on tumor cells.
