AB170. Quercetin inhibits angiogenesis through thrombospondin-1 up-regulation to antagonize human prostate cancer PC-3 cell growth in vitro and in vivo

OBJECTIVE: To explore the important role of TSP-1 up-regulation in inhibiting angiogenesis and anti-prostate cancer effect of quercetin both in vitro and in vivo for the first time. METHODS: Human prostate cancer androgen-independent PC-3 cells and Human umbilical vein endothelial cells (HUVECs) were cultured with vary dose of quercetin for certain time. PC-3 cells were inoculated subcutaneously in male BALB/c nude mouse. When xenograft tumors reached about 100 mm(3), mouse were randomly allocated and treated. Tumor size and mouse weight were recorded. Relevant biomarkers of cells and tumor tissues were analyzed. RESULTS: After the varied doses were used for a certain time, quercetin (I) significantly inhibited PC-3 and (HUVECs) proliferation, migration and invasion in a dose dependent way; (II) effectively inhibited prostate cancer PC-3 cells xenograft tumor growth by 37.5% with 75 mg/kg as compared to vehicle control group, more effective than 25 (22.85%) and 50 mg/kg (29.6%); (III) was well tolerated by BALB/c mice and no obvious toxic reactions were observed; (IV) greatly reduced angiogenesis and led to higher TSP-1 protein and mRNA expression both in vitro and in vivo in a dose dependent way. CONCLUSIONS: Therefore, quercetin could increase TSP-1 expression to inhibit angiogenesis resulting in antagonizing prostate cancer PC-3 cell and xenograft tumor growth. The present study can lay a good basis for the subsequent concrete mechanism study and raise the possibility of applying quercetin to clinical for human prostate cancer in the near future.