β-elemene reverses hepatocyte growth factor-induced resistance to ge-fitinib in PC-9 lung cancer cells via c-Met pathway / 中国病理生理杂志

ABSTRACT

AIM:To investigate the effect of β-elemene on reversing hepatocyte growth factor(HGF)-induced resistance to gefitinib in PC-9 cells, and to explore its possible mechanisms.METHODS: The gefitinib-resistant PC-9 cells induced by HGF were treated with β-elemene or/and gefitinib.The cell activity was measured by MTT assay.The effect of β-elemene on the invasion ability in HGF-induced resistance to gefitinib in PC-9 cells was detected by Transwell migration assay.The protein levels of p-Met, c-Met, p-AKT and AKT in PC-9 cells of each group were determined by Western blot.RESULTS:The results of MTT assay showed that the cell activity of PC-9 cells was significantly inhibited by β-elemene(P<0.05).IC50of β-elemene for PC-9 cells was 169.31 mg/L.IC50of gefitinib for PC-9 cells was 0.30 μmol/L.Exogenously adding recombinant HGF induced significantly resistance to gefitinib in PC -9 cells.Moreover, SU11274(an inhibitor of c-Met)significantly decreased the viability of the cells exposed to HGF and gefitinib(P <0.05).Combined treatment with β-elemene and gefitinib in the presence of HGF(50 μg/L)significantly decreased the viability of PC-9 cells as compared with the PC-9 cells treated with gefitinib alone in the presence of HGF(P<0.05),so did the result of the cell migration.The protein levels of p-Met and p-AKT were significantly up-regulated by HGF,while the protein levels of p-Met and p-AKT were markedly down-regulated in the cells treated with β-elemene and gefitinib com-pared with gefitinib alone in the presence of HGF.CONCLUSION: β-elemene reverses HGF-induced resistance to ge-fitinib in lung cancer PC-9 cells,likely due to the inhibition of HGF-induced activation of c-Met and its down streams sig-naling pathways(P<0.01).