橙皮苷对人肝癌HepG2细胞增殖抑制与凋亡诱导作用的机制OA

Objective To investigate the inhibitory effects of hesperidin on the proliferation of human hepatocel-lular carcinoma HepG2 cells and its apoptosis-inducing activity,and to systematically elucidate the underlying molecular mechanisms,thereby providing experimental evidence for the development of natural product-derived therapeutic agents for liver cancer.Methods HepG2 cells were cultured in vitro and divided into a control group(cultured in normal medi-um)and hesperidin treatment groups with gradient concentrations(8,16,24,and 32 μmol/L).After 24 h of treatment,multiple experimental approaches were used to evaluate key indicators.Cell proliferation inhibition was assessed using the Cell Counting Kit-8(CCK-8)assay.Changes in mitochondrial membrane potential(△Ψm)were detected using the JC-1 fluorescent probe.Caspase-3 activity was measured by enzymatic assay.Intracellular reactive oxygen species(ROS)levels were quantified using the DCFH-DA fluorescent probe.Results Hesperidin treatment reduced HepG2 cell viability in a concentration-dependent manner,with survival rates of 77.60％(8 μmol/L),68.23％(16 μmol/L),58.21％(24 μmol/L),and 50.36％(32 μmol/L).Compared with the control group,hesperidin-treated HepG2 cells exhibited increased mitochondrial depolarization,as indicated by a fluorescence shift from red to green.Caspase-3 activi-ty was significantly increased following hesperidin treatment,reaching 124.64％(8 μmol/L),134.91％(16 μmol/L),142.05％(24 μmol/L),and 160.44％(32 μmol/L)relative to the control group.(4)Intracellular ROS production in-creased progressively after hesperidin exposure,reaching 106.51％(8 μmol/L),119.78％(16 μmol/L),163.36％(24 μmol/L),and 245.94％(32 μmol/L).Conclusion Hesperidin inhibits the proliferation of HepG2 cells and in-duces apoptosis by increasing ROS production,triggering mitochondrial dysfunction,and activating Caspase-3.These findings suggest that hesperidin may serve as a promising natural product candidate for targeted therapy against hepatocel-lular carcinoma.