Inhibition and Related Mechanism of Nobiletin in Experimental Metastasis of Melanoma Cells in Mice

The anti-metastasis effect of nobiletin was investigated using experimental lung metastasis model mice by injection of melanoma cells K111 from caudal vein. The influence of nobiletin on amount of gelatinases MMP2 and MMP9 secreted by K111 cells in vitro was also tested. The results showed that nobiletin could effectively inhibit the experimental lung metastasis of melanoma cells,the inhibition rate against metastasis was 47.3% at 32mg/kg. The results of gelatin zymography showed that the secretion of the MMP2 and MMP9 was decreased at the drug concentration of 125 and 62.5μmol/L,the expression rates of the two groups were about 30% and 50%, compared with the control. Real time PCR assay demonstrated that mRNA level of MMP2 and MMP9 in K111 cells treated with 125μmol/L nobiletin was also lower than that of the control. The results indicated that nobiletin could down-regulate the expression of MMP2 and MMP9 at transcriptional level and metastasis as well in mice model.