| Melanoma is a common skin tumor induced by abnormal melanocytes hyperplasia, with the high degree of malignancy, accounting for the vast majority of patients died of skin tumors. The incidence of melanoma in China is increasing year by year. Several therapeutic method, such as operation, medication, chemotherapy and radiotherapy, are the main ways of melanoma treatment. Unfortunately, the result is not good enough and the5-year survival rate of melanoma below5%. The main reason of bad treatment and death is associated with tumor metastasis. Thus, to find a natural plant chemical active component can inhibit metastases of malignancy, has become the research focus of the prevention and treatment of tumorFlavonoids are common in nature and the good anti-tumor effect have been demonstrated by a lot of researchs. The the main mode of action of its anti-tumor including inhibiting tumor cell proliferation, new blood vessel formation, invasion and metastasis, and so on. Liquiritigenin is a flavanone extracted from Glycyrrhizae, Studies have shown that liquiriticnin has antispasmodic. anti-inflammatory, antibacterial, anti-ulcer and other pharmacological effects. The previous study in our laboratory shown that liquiritigenin can suppresses the proliferation of human hepatocarcinoma cell line(SMMC-7721) and human cervical cancer Hela cells. In vitro, liquiritigenin can suppresses the migration of human lung adenocarcinoma cell line(A549) through the PI3K/Akt signaling pathway. However, whether liquiritigenin inhibits the migration of tumor in vivo and its underlying molecular mechanisms remain unclear. In the present study, we investigated the effect of liquiritigenin on tumor migration and the possible signaling pathway also been detection. Objective:This study was aimed to elucidate the effects of liquiritigenin on melanoma migration in C57BL/6mice.Methods:Established the experimental lung metastasis models, C57BL/6mice were randomly divided into different groups. Mice were gavage with liquiritigenin at different doses. Animals were sacrificed21d after tumou injection. Lungs were removed and weight, Metastastic foci at lung surfaces were photographed and counted, calculated the lung index and inhibition ratio of lung metastasis. Fixed the lungs and maked immunohistochemical analysis.Results:(1) The result indicated that average weight of model control group weighs than blank control group(p<0.01) and all liquiritigenin groups(p<0.05), the result in a dose-dependent manner.(2) The lung index of model control group was high than other groups, the result in a dose-dependent manner(p<0.05), the result in a dose-dependent manner.(3) The number of foci on the lung surface of model control group was high than other groups (p<0.05)and the inhibition ratio of lung metastasis of liquiritigenin groups were high than model control group(p<0.05), the result in a dose-dependent manner..(4) The result of HE staining shows that liquiritigenin could keep the structures of lung and decrease the melanoma focal.Conclusion:liquiritigenin can significantly inhibit melanoma migration in C57BL/6. Objective: The aim of our study was to explore the molecular mechanisms of liquiritigenin inhibit the migration of melanoma. Methods:Enzyme linked immunosorbent assay and western blot assay were detect the excretion and expression of MMP-2/9. The effects of liquiritigenin on the P13K/Akt/NF-kB pathway was examined by western blot assay.Results:Compare to model control group,the liquiritigenin groups(7.5,15,30mg/kg)(1) Liquiritigenin significantly reduced the secretion of MMP-2/9in serum, the result in a dose-dependent manner.(2) The results showed that the treatment of liquiritigenin inhibitied the protein level of MMP-2/9, NF-Kb(nucleus), phosphorylation of Akt, PI3K. Meanwhile, liquiritigenin inhibited the ratio of NF-κB(nucleus): NF-κB(cytosol). All of above-mentioned were in a dose-dependent manner.Conclusion:Liquiritigenin might inhibit MMP-2/9expression of melanoma in C57BL/6mice through the P13K/Akt/NF-KB pathway. |
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