Phenotypic resistance to anti-VEGFR therapy in a SKOV-3 ovarian cancer xenograft mouse model.

<p><b>A)</b> SKOV-3 xenografts were treated for eight weeks with 30 mg/kg sorafenib via daily oral gavage. Controls were treated with the treatment vehicle alone. Tumor volumes were measured twice a week and are represented as mm³ ± SEM. Out of 19 mice, 10 developed resistance to the sorafenib treatment. Black, red, and green lines indicate the mean tumor volume progressions of control, SR, and SS mice, respectively. A significant difference in tumor volume (* <i>P</i> < 0.05) was observed between the treatment-resistant and-sensitive groups, starting at week five of treatment. SS = sorafenib-sensitive; and SR = sorafenib-resistant. B) Representative immunostaining for CD-31 (top row), and Ki-67 (bottom row) in control, sorafenib-sensitive (SS), and sorafenib—resistant (SR) tumors. C) Vessel density (CD-31) and proliferation index (Ki-67) were significantly increased in sorafenib-resistant tumors compared with the sorafenib-sensitive tumors.