Abstract
PURPOSE: The aim of the study was to evaluate the effect of the agent SU-11248 (sunitinib malate) in the course from non-castration to castration LNCaP xenograft prostate tumors. METHODS: BALB/c nude mice were injected with human androgen-dependent prostate cancer cell line (LNCaP) and divided into two groups: castration and non-castration. Then the LNCaP-bearing mice were treated with sunitinib (40 mg/kg daily, 0.2 ml p.o. for 3 weeks). Both groups were paired with control groups in which the mice were given water by gavaging daily. The kidneys, livers, hearts, lungs, spleens, stomachs, intestines, skins, and other parts of all the mice were observed carefully during the study. RESULTS: At the end of the 3-week dosing schedule, the tumors of the sunitinib-treated mice grew significantly slower than those of control group. Adverse reactions were not significantly found in the mice. We examined the impact of sunitinib on tumor growth and tumor angiogenesis through molecular factors representative of vascular endothelial growth factor receptors (VEGFR-2) and platelet-derived growth factor receptors (PDGFR-β) families, and of apoptosis (Bcl-2), and of proliferation (Ki67). The Ki67 and Von Willebrand factor expression of the control group was higher than that of the treated group. However, there was no significant difference observed between treated and control groups for apoptosis induction (Bcl-2). Immunohistochemistry, Western blot, and quantitative polymerase chain reaction results showed both VEGFR-2 and PDGFR-β expression in the control group was higher than that of the sunitinib-treated group. CONCLUSION: Sunitinib is safe and effective for treating tumors in the course form non-castration to castration groups in LNCaP xenograft prostate tumors. It is potentially beneficial as a prevention and treatment measure for clinical patients with prostate cancer, especially in the course from androgen-dependent prostate cancer to castration-resistant prostate cancer.