Sorafenib inhibits angiogenesis without blocking metronomic CPA-induced tumor regression. A) Mice bearing 9L tumors were drug-treated, as indicated, with tumor volumes normalized to 100% at the first day of treatment (day 0), when group averages reached ~500 mm3 (n = 12 tumors/group). Drug treatments: sorafenib (25 mg/kg, i.p. daily for 24 or 36 days, as marked, and metronomic CPA (140 mg/kg i.p. every 6 days for 11 cycles; days 0–60). Data shown are normalized tumor volumes, mean ± SE for n = 10-12 tumors/group. CPA vs. CPA + Soraf: p > 0.05 by 1-way ANOVA. B) Representative CD31 immunostaining images of tumors treated as in A and excised on treatment day 24. ImageJ quantification is shown below, mean ± SE based on n > 20 images/treatment group, with **, p < 0.01; ***, p < 0.001 vs. untreated (UT) controls by 1-way ANOVA. C) Phospho-VEGFR2 immunostaining (brown) with hematoxylin counterstaining (purple) of 9L tumors collected from mice either 2 or 4 hr after a single injection of DC101, sorafenib, or axitinib, or from untreated (UT) tumors (see Methods). Blue arrows, phospho-VEGFR blood vessels; red arrows, unstained blood vessels. Results are based on >20 images taken over two independent sections in each of 4 tumors per treatment group. Results shown are representative of at least two separate sets of analyses. See Additional file 4 for additional images.