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 mm³, 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.

Keywords: Quercetin; prostate cancer; angiogenesis inhibition; thrombospondin-1 up-regulation