Background: Sunitinib is an inhibitor that blocks tyrosine phosphorylation (p-Tyr) of receptors including vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor. Sunitinib suppresses angiogenesis and cell proliferation and is an effective treatment for renal cell carcinoma and gastrointestinal stromal tumors. In the present study, we examined the antitumor and antimetastatic activities of sunitinib in mouse metastatic mammary cancer.
Materials and methods: Mammary tumors induced by inoculation of BJMC3879 cells into mice were treated with sunitinib using mini-osmotic pumps. At 1 week and 7 weeks after initiation of drug administration, cancer tissue was removed and carried out histopathological and immunohistochemical examination.
Results: Tumor growth, as well as metastasis to the lungs and other organs, was significantly inhibited in sunitinib-treated mice. Cell death areas in mammary carcinomas were much larger in the sunitinib-treated groups than in the control group. In addition, sunitinib induced necrotic cell death rather than apoptosis. Although microvessel density was significantly lower in the sunitinib-treated mammary tumors, numbers of metastases to lymph nodes and the number of lymphatic vessels in the mammary tumors were not significantly different among groups. Cell proliferation, as assessed by BrdU-labeling indices, was significantly lower in mammary carcinomas of sunitinib-treated mice. The amounts of p-VEGFR-2 and p-Tyr, as determined by immunohistochemistry, were greatly reduced in sunitinib-treated mice.
Conclusion: In a mouse model of mammary cancer, sunitinib inhibited tumor growth and metastasis (with the exception of lymph node metastasis), angiogenesis, and cell proliferation possibly due to reduced levels of p-VEGFR-2 and p-Tyr.