Effect Of Grape Procyanidins On Tumor Angiogenesis In H22Liver Cancer Xenograft Models

To study the effects of Grape Proanthocyanidins (GPC) on the growth and angiogenesis of hepatocellular carcinoma H22cells xenograft in mice.Methods:The xenograft model established using by injected subcutaneously H22cells into the right axilla of the mice. Each group was treated with different doses of Grape Proanthocyanidins (GPC)and Endostar. All these treatments were maintained for10days,and mice were sacrificed. The xenograft tumors in mice were measured. The proliferation activity level of H22cells was determined by MTT assay.The expression levels of vascular endothelial growth factor (VEGF) protein and micro vessel density(MVD) were examined by immunohistochemistry,and VEGF mRNA was examined by real-time PCR in tumor tissue.Results:When treated with50,200mg/Kg of GPC,200mg/Kg GPC combined Endostar and Endostar, the tumor inhibition rates were13.17%,23.37%,36.15%and14.71%, respectively. The tumor weight of xenograft was significantly lighter in the combined group than the control group(P<0.05). The OD decreased in the high GPC group and the combined group,which were statistically significant(P<0.01). The expression of MVD, VEGF and VEGF mRNA decreased gradually as the concentration of GPC increased,which were statistically significant(P<0.05compared with the control group and the low GPC group).There was statistically significance of the expression of MVD,VEGF protein and VEGF mRNA between the combined group and the high dose GPC group (P<0.05).Conclusions:GPC can inhibit the growth of hepatocellular carcinoma H22cell xenografts in mice. The inhibition of angiogenesis may play a key role in the anti-neoplastic effect of Grape Proanthocyanidins (GPC).