Effects of tangeretin on growth and invasion of human non-small-cell lung cancer cells

AIM: To study the influences of tangeretin(TGN) on the growth and invasion of non-small-cell lung cancer( NSCLC) cells,and to explore the molecular mechanisms. METHODS: The A549 cells were treated with different concentrations of TGN in vitro. The relative cell activity was determined by MTT assay. The apoptotic rate was analyzed by flow cytometry with Annexin V-FITC / PI staining. The number of the invasive cells was measured by Transwell assay. The mRNA expression of MMP-2 and MMP-9 was detected by RT-PCR,and the protein levels of Ki67,Cyt C,caspase-3,cleaved caspase-3,MMP-2,MMP-9,Akt,p-Akt and p-PI3 K were determined by Western blotting analysis.RESULTS: TGN inhibited the proliferation of A549 cells in a dose-dependent manner( P 0. 05) along with the low expression level of proliferation biomarker Ki67. TGN up-regulated the protein levels of Cyt C,caspase-3 and cleaved caspase-3( P 0. 01) and promoted the apoptosis of A549 cells in a dose-dependent manner. Moreover,TGN down-regulated the invasion-related molecules MMP-2 and MMP-9 at the mRNA and protein levels,and the number of invasive cells reduced with the increase in the concentration of TGN. The protein levels of p-Akt and p-PI3 K in the A549 cells was reduced( P 0. 05),and no difference of the cell viability in the cells treated with different concentrations of TGN was observed after blocking PI3 K / Akt signaling pathway using LY294002. CONCLUSION: TGN inhibits the growth and invasion of A549 cells and promotes the cell apoptosis by potentially inhibiting PI3 K / Akt signaling pathway activation. Therefore,this study will provide a new target for the prevention and control of NSCLC.