| OBJECTIVE: Ursolic Acid is a triterpenoid ubiquitous in nature with lots of biological effects of which anti-inflammatory and anti-tumor are the most concerned ones. However, the mechanism of the anti-tumor effect is remained unclear. Tumor angiogenesis is critical to tumor growth. Drugs targeted at important steps of tumor angiogenic process become popular in research area. UA has already acclaimed for its in vivo inhibitory effect in the CAM assay which implied its potential of becoming an anti-angiogenic drug. Our aim is to investigate the effect of UA on vascular endothelial growth factor (VEGF), the key stimulator of the angiogenic process. Explore the mechanism of anti-angiogenesis of UA.METHOD: HepG2 cells were cultured under hypoxia environment induced by CoCl2. After the treatment of UA, the VEGF level in the culture medium was measured by ELISA, the mRNA level of VEGF was measured by real-time PCR. At the same time, the xenografts derived from HepG2 cells were established in BALB/C-nude mice. The mice were divided into UA group, solvent control group and control group. After corresponding treatments of UA, the expression of VEGF was measured by western blot and the tumor inhibition rate was evaluated. In addition, slices of the tumor were made to be examined with HE method as well as the electron microscope.RESULTS: mRNA of VEGF was greatly inhibited in a dose-depended manner in HepG2 cells; however, the expression of VEGF was up-regulated. The tumor growth was slightly inhibited and the protein level of VEGF was (3.11±0.55) times increased by the control group(P<0.05). HE as well as electron microscope inspection showed UA has anti-angiogenic anti-tumor effect.CONCLUSION: Ursolic acid can inhibit the tumor growth and down-regulate the mRNA of VEGF, but up-regulate the expression of VEGF, exhibiting two-way effect and complexity. The different signs of the effects on angiogenesis force one to further research on its anti-angiogenic potential.
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