Anti-tumor Effect Of β-elemene In Murine Hepatocellular Carcinoma Cell Line H22Depends On The Level Of C-Met Downregulation

Objective:β-elemene, extracted from ginger plant Rhizoma zeodaria, exerts anticancer effectin a variety of tumor diseases including liver cancer. Previous reports on β-elemenehave been shown that it can inhibit tumor cells growth in vitro and in vivo and havebeen put into clinical trials in cancer patients in China. No bone marrow suppressionand drug resistance have been observed in the clinical studies; on the contrary, patientimmunity was improved during therapy with β-elemene.c-Met, as a tyrosine kinase receptor, encoded by an oncogene, is essentialcomponent that participate in the cell proliferation and is activated to induce an invasiveprogram consisting of cell proliferation, migration, invasion, survival, and branchingmorphogenesisis. The receptor tyrosine kinase c-Met often implicated in a variety ofmalignancies and widely found overexpressed in neoplastic tissues. Conversely, thedown-regulation of c-Met in cancer cells endogenously expressing c-Met decrease theirtumorigenic potential.To explore the mechanism of action of β-elemene in cancer, we identified whetherthere is some relations between the expression level of c-Met and anticancer action ofβ-elemene.Methods:The presence of c-Met in the H22cells was confirmed by RT-PCR, Westernblotting and Immunofluorescence analysis. In vitro, H22cells were treated withβ-elemene for different time and the expression of c-Met in H22cells was measured byRT-PCR, Immunofluorescence analysis and Western blotting. In vivo, an experimentalH22hepatocellular carcinoma (HCC) xenograft transplantation model, treated withdifferent dose-dependent β-elemene, the expression of c-Met was measured by RT-PCR, Immunohistochemical staining assay.Results:c-Met was found highly expressed in H22cells than that in murine liver cells;after treating with β-elemene for48h, the expression of c-met decreased markedly inH22cells; furthermore, we showed that high-dosage β-elemene group significantlyreduced tumor weights and down-regulated the expression of c-Met compared to NScontrol group in H22transplanted tumor.Conclusions:Down-regulation of c-Met expression by β-elemene induces growth inhibition inMurine Hepatocellular Carcinoma.