Abstract: Objective To investigate the effect of genistein on cholesterol metabolism and SREBP-2 pathway in HepG2 cell.Methods HepG2 cells were cultured with 0, 0.01, 0.10, 1.00, 10.00, 50.00, and 100.00 μmol/L of genistein for 24, 48, and 72 hours, respectively.Then, the cell proliferative activity was detected by MTT.HepG2 cells were incubated with 0, 0.01, 1.00, 10.00, and 50.00 l/L genistein for 24 hours and then collected for the cholesterol determination.The gene expression levels of ldlr and hmgcr were measured by real-time quantitative PCR.The expression of nuclear transcription factor SREBP-2 was determined by Western blotting.ResultsAfter incubation with genistein for 24 hours, the proliferative rates of cells treated with 0.01, 0.10, and 1.00 μmol/L genistein were higher than that of the control (P<0.05 for all).However, after incubation with genistein for 48 or 72 hours, the proliferative rates of cells treated with 1.00, 10.00, 50.00, and 100.00 μmol/L genistein were lower than that of the control (P<0.05 for all).Cholesterol levels in HepG2 cells incubated with 1.00, 10.00, and 50.00 μmol/L genistein for 24 hours were［1.81±0.15］,［2.29±0.17］, and［2.88±0.08］mmol/L, respectively, which were higher than that of the control cells (［1.44±0.17］mmol/L).There was a rising trend as the genistein concentration increased (R2=0.48，P<0.01).Meanwhile, mRNA levels of hmgcr and ldlr were also increased as the genistein concentration increased (R2=0.53 or 0.79,P<0.01 for all).SREBP-2 protein levels in HepG2 cells incubated with 1.00, 10.00, and 50.00 μmol/L genistein were much higher than that in control cells (P<0.01 for all).Conclusion Genistein could regulate the cholesterol metabolism in HepG2 cells and its mechanism may be related to regulating gene or protein expressions involved in the SREBP-2 pathway.