SBF-1 strongly inhibited the growth of both ARWT and ARmutant prostate cancer in nude mice
Finally, the effect of SBF-1 on prostate cancer growth in vivowas tested. Nude mice were injected s.c. with LNCaP or PC3/AR+ cells. After the tumor reached 50 mm3, SBF-1 was administered i.p. at 10 and 30 µg/kg. SBF-1 significantly reduced the tumor size in mice, in a dose-dependent manner (Fig. 6A and B). At the end of treatment, animals were injected with ICG dye-conjugated IGF-1 antibody and after 3 hours from injection, the tumor size and the fluorescent intensity were measured. SBF-1 dramatically reduced both tumor size and the fluorescent intensity of IGF-1 in mice at such very low doses in a dose-dependent manner, suggesting a relation of the strong inhibition of tumor growth to the reduced IGF-1 expression (Fig. 6C-F). In this case, SBF-1 significantly avoided the decrease in body weights of mice bearing tumor (Fig. 6G and H) and prolonged the survival rate (Fig. 6I and J). In addition, SBF-1 inhibited the expressions of pARS515, pAKTS473, pFOXO1S256, IGF-1, PCNA, and Bcl-2 proteins extracted from the tumor tissues in both models (Fig. 6K and L).