Figure 3

Effect of sunitinib on nude mice engrafted with MDA-MB-231 and MCF-7 cells. A) Tumor growth curves of (N = 20 per group). B) Microcirculation patterns. The number of EDVs decreased in sunitinib-treated mice with MDA-MB-231 tumors, and more VM channels were observed during and after these mice were treated with sunitinib compared with mice bearing MDA-MB-231-induced tumors that received placebo. The EDVs rebounded after the treatment of mice with MDA-MB-231 tumors. VM channels did not form in mice with MCF-7 tumors. The arrows indicate the VM channels formed by PAS-positive matrix and tumor cells. C) Immunofluorescence analysis of endomucin and CD133 expression and Hydroxyprobe analysis of oxygen levels. More Hypoxyprobe-positive cells were observed in the mice with tumors formed by MDA-MB-231 and MCF-7 tumors treated with sunitinib compared with those in the control group. The hypoxic area in tumors formed by MDA-MB-231 cells disappeared when treatment was terminated, and EDVs rebounded upon treatment. Conversely, there was no significant difference between mice with tumors formed by MCF-7 cells during or after treatment with sunitinib. CD133⁺ cells were present in MDA-MB-231 tumors in the center and periphery of the hypoxic area. The number of CD133⁺ cells in MCF-7 tumors did not differ among groups. D) Quantification of VM. VM channels were not observed in MCF-7 tumors. E) Quantification of EDVs. F) Quantification of CD133⁺ cells. More CD133⁺ cells were present in the MDA-MB-231 tumors in mice treated with sunitinib compared with those in other tumors. Scale bar = 100 μm, and the error bar indicates the SD.