Figure 6.

Ursolic acid inhibits breast cancer growth and metastasis in zebrafish and mouse xenotransplantation models of breast cancer without observable toxicities. (A) The juvenile zebrafish bearing the Dil-stained breast cancer MDA-MB-231 cells were treated with 10~20 μM ursolic acid for 48 h The proliferation and dissemination of the injected MDA-MB-231 cells in the zebrafish breast cancer xenotransplantation model were observed under a stereomicroscope. N = 3. (B, C) The 4T1-Luc breast cancer xenograft model was established by subcutaneously injecting 4T1-Luc cells into the mammary fat pads of mice. Ursolic acid administration (25~50 mg/kg/d) by intraperitoneal injection suppressed the growth and lung metastasis of 4T1-Luc xenografts in mouse breast cancer xenotransplantation models. N = 6. Scale bar = 100 μm. (D) The hepatotoxicity, nephrotoxicity and hematotoxicity of ursolic acid in mice were detected by biochemical analysis. N = 3. (E, F) Tissue immunofluorescence assay (E) and Western blotting assay (F) were conducted to investigate the effect of ursolic acid on the expression levels of LDH-A, c-Myc, SP1 and Cav-1 in mammary tumor tissues. N = 3. Scale bar = 20 μm. (G) The effect of ursolic acid on glycolytic metabolism of primary breast cancer cells was investigated by measuring ECARs. N = 3. ^* p < 0.05. ^** p < 0.01.