The Inhibitory Effect Of Grape Proanthocyanidins On Metastasis Of Breast Cancer

Objective To study the inhibition of grape proanthocyanidins(GPC) on metastasis of breast cancer, we detected the expression of MMP-2,phosphorylation of P38MAPK(P-P38MAPK) and c-fos protein.Methods After inoculating EMT-6 breast cancer cells in right mammaria area, 40 Balb/c famale mice were divided into tumor control,low,middle and high dose of GPC groups at radom. The three GPC groups were given 10,100 and 200 mg/kg by mouth once a day. The tumor control group were given equal dose of normal sodium(Ns.). After two weeks, MMP-2,phosphorylation of P38MAPK(P-P38MAPK) and c-fos protein were detected by Westernblot and immunohistochemistry.Results Western blot showed that the levels of MMP-2 protein in 100 and 200mg/kg GPC groups and tumor control group were 0.73±0.04,0.69±0.04 and 0.98±0.04 respectively. The expression of P-P38MAPK in the three groups were 0.63±0.15,0.58±0.12 and 1.16±0.18 respectively. The results of c-fos protein by immunohistochemistry showed that ratios of positive cells in 100 and 200mg/kg GPC groups were 0.22±0.04 and 0.20±0.05, in tumor control group was 0.36±0.04. The levels of all the detective targets in 100 and 200mg/kg GPC groups were lower than those in tumor control group. The differences were significantly (P＜0.05). But there was no significant differences between 10mg/kg GPC group and tumor control group(P＞0.05).Conclusion GPC can inhibit the expression of MMP-2 protein so that it has a remarkable inhibitory effect on the matastasis of breast cancer. The proboble mechanism is that GPC inhibit the level of P-P38MAPK and c-fos protein that results in a reduced synthesis of MMP-2 protein.