Genistein Exerts Anti-tumor Effects In Small Cell Lung Cancer Cell Via Suppressing The Activity Of FoxM1Pathway

Part I:Genistein leads to decrease of small cell lung cancer cell proliferation and migration abilityObjective:To investigate the influence of genistein on the proliferation and migration ability of SCLC cell line H446.Methods:Human SCLC cell line H446were treated with various concentrations of genistein. CCK-8assay, Flow cytometric analysis, wound healing assay were used to investigate the influence of genistein on cell growth, apoptosis, cell cycle progression and migration ability of H446cells.Results:After exposure to various concentrations of genistein for24h,48h and72h, the proliferation of H446cell was significantly inhibited in a dose-dependent and time-dependent manner. H446cell was treated with25,50and75μmol/L genistein for72h. After treatment, the degree of apoptosis was found to be increased, accompanied by G2/M phase cell cycle arrest. The induction of apoptosis and G2/M phase cell cycle arrest was also dose-dependent (P<0.05). Morever, the migration ability of H446cell after genistein treatment was dramatically inhibited, as manifested by wound healing assay.Conclusion:Genistein leads to inhibition of the proliferation, induction of apoptosis and G2/M phase cell cycle arrest and decreased migration ability of SCLC cell, suggesting that genistein could be an effective medicine for the treatment of SCLC. Part II:The study on the molecular mechanisms by which genistein exerts anti-tumor effectsObjective:Our previous study suggested an anti-tumor effect of genistein in SCLC. However, the molecular mechanisms by which genistein elicits its effect were not clear. Therefore, the purpose of the current study was to investigate the anti-cancer mechanisms of genistein.Methods:H446cell was treated with25,50and75μmol/L genistein for72h. Real-time PCR and Western blot analysis were used to detect the expression of FoxM1and its downstream target genes. The FoxM1cDNA plasmid transfection was performed to up-regulate FoxM1. CCK-8assay was used to evaluate the influence of up-regulation of FoxM1on cell proliferation.Results:Genistein led to attenuation on FoxM1and decrease of its downstream genes, such as cdc25B,cyclinBl, survivin, whereas p21expression was increased (P<0.05). We also found that up-regulation of FoxM1by cDNA transfection prior to genistein treatment reduced genistein-indueed cell proliferation inhibition (P<0.05).Conclusion:Genistein inhibits the proliferation of SCLC cell which is partly mediated through suppressing the activity of FoxM1pathway...