Abstract:

Objective   To investigate the influence of genistein on the growth of small cell lung cancer(SCLC) cell line H446 and the underlying molecular mechanisms. Methods   Human SCLC cell line H446 were treated with various concentrations of genistein(10，25，50，75，100μmol/L). CCK-8 assay, Flow cytometric analysis, Real-time PCR and Western blotting analysis were used to investigate the influences of genistein on cell growth, apoptosis, cell cycle progression and the mRNA and protein alterations of FoxM1 pathway. Results   Genistein significantly inhibited the proliferation of H446 cells, accompanied by apoptosis and G2/M phase cell cycle arrest (P<0.05). Importantly, genistein led to attenuation on FoxM1 and decrease of its downstream genes, such as survivin, cyclin B, cdc25B, whereas p21 expression was increased (P<0.05). We also found that up-regulation of FoxM1 by cDNA transfection prior to genistein treatment reduced the inhibition of genistein-induced cell proliferation(P<0.05). Conclusion   Genistein inhibits the proliferation of SCLC cells which is partly mediated through suppressing the activity of FoxM1 pathway.

Key words: Lung neoplasms， small cell； Genistein； FoxM1； Cell cycle arrest； Apoptosis； Antitumor