TZDs have direct and indirect antiangiogenic effects. (a) Percent proliferation of BCE cells is determined by comparing cells exposed to an angiogenic stimulus (bFGF) with those exposed to bFGF and rosiglitazone, relative to unstimulated cells (low serum), in a 72-hour proliferation assay. Percent proliferation of tumor cells is determined by comparing cells exposed to 10% FBS with those exposed to 10% FBS and rosiglitazone, relative to starvation conditions (0.5% FBS). In both cases, percent proliferation = 100 × (cells_{stimulated+TZD} – cells_{low serum})/(cells_stimulated – cells_{low serum}). Each point represents the mean ± SD for three wells. Representative experiments of three separate assays are shown. The difference in inhibition between day 3 and day 7 is a result of increased endothelial cell death on day 7 in unstimulated cells in starvation media (cells_{low serum}). (b) Percent of proliferation for endothelial and tumor cells treated for 7 days with rosiglitazone. (c) Levels of the phosphorylated form of eIF-2α protein upon treatment with rosiglitazone in HUVECs. NIH3T3 fibroblasts (3T3) serve as a positive control. (d) VEGF levels (expressed as percent decrease) in U87 and LLC cells after 6 days of treatment with rosiglitazone.