Effects of TNF-alpha and curcumin on the expression of VEGF in Raji and U937 cells and on angiogenesis in ECV304 cells.

BACKGROUND: To better understand the possibilities of antiangiogenic tumor therapy and to assess possible side effects, we investigated the effect of tumour necrosis factor (TNF)-alpha and curcumin on the expression of vascular endothelial growth factor (VEGF) in U937 and Raji cell lines and their effect on angiogenesis in a human umbilical vein endothelial cell (HUVECs)-derived cell line (ECV304), and also the relationship between Notch1 and VEGF. The aim of this study was to elucidate potential mechanisms controlling tumor neovascularization. METHODS: VEGF secreted by U937 and Raji cell lines was determined by ELISA. Angiogenesis was tested by network formation of endothelial cells on Matrigel. Levels of VEGF mRNA in U937 and Raji cells and Notch1 mRNA levels in EV304 cells were determined by RT-PCR. RESULTS: Secretion of VEGF by U937 and Raji cells was increased by TNF-alpha treatment and suppressed by curcumin (P < 0.01). The mRNA expression of VEGF165 and VEGF121 (containing 165 and 121 amino acid residues, respectively) were detected in any fractions. TNF-alpha augmented the expression of VEGF165 and VEGF121 mRNA and curcumin reduced the expression (P < 0.01). No networks or cords formed in control and curcumin groups. There was tube formation on matrigel in the supernatants of the Raji culture group and the supernatants groups treated by VEGF group and TNF-alpha in Raji cell. Notch1 mRNA was detected but there was no significant change in the VEGF group compared with control (P > 0.05). CONCLUSIONS: Expressions of VEGF mRNA in U937 and Raji cells were increased by TNF-alpha and suppressed by curcumin. VEGF and TNF-alpha can induce angiogenesis, and curcumin can inhibit angiogenesis in ECV304 cells.