Molecular mechanisms underlying the inhibitory effects of mollugin on cervical cancer cell proliferation,adhe-sion,and glycolysis via the PI3K/AKT pathway

ZHAO Bo; WANG Ying; WANG Xian-hong

doi:10.13820/j.cnki.gdyx.20243258

Abstract：Objective To investigate the regulatory effects of mollugin on the proliferation,adhesion,glycolytic activity,and PI3K/AKT signaling pathway in human cervical cancer cells.Methods Human cervical cancer HeLa cells were cultured in vitro and treated with various concentrations of mollugin(0,12.5,25,50,and 100 μmol/L).The cell viability was assessed using the CCK-8 assay to determine the optimal concentration,which was found to be 50 μmol/L.HeLa cells were then divided into five groups,Control Group(0 μmol/L mollugin),Experimental Group(50 μmol/L mollugin),Positive Drug Group(20 μg/mL 5-fluorouracil),Activator Group(50 μmol/L mollugin+10 μmol/L PI3K/AKT pathway activator SC-79)and Inhibitor Group(50 μmol/L mollugin+2 μmol/L PI3K/AKT pathway inhib-itor LY294002).All treatments were applied for 24 hours.Cell proliferation was measured using the EdU assay;cell ad-hesion was evaluated via adhesion experiments;lactate and glucose levels were determined using specific assay kits;and the expression levels of key proteins-including hexokinase 2(HK2),lactate dehydrogenase A(LDHA),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),phosphorylated PI3 K(p-PI3 K),and phosphorylated AKT(p-AKT)-were analyzed by Western blotting.Results The CCK-8 assay confirmed that 50 μmol/L was the optimal concentration of mollugin for intervention.Compared to the control group,both the experimental and positive drug groups exhibited signifi-cant reductions in cell proliferation,adhesion,lactate and glucose levels,and protein expression levels of HK2,LDHA,GAPDH,p-PI3K,and p-AKT(P＜0.05).Furthermore,the inhibitor group showed a further significant decrease in these indices compared to the experimental group(P＜0.05),whereas the activator group exhibited a significant increase in these parameters relative to the experimental group(P＜0.05).Conclusion Mollugin exerts an inhibitory effect on HeLa cell proliferation,adhesion,and glycolytic activity by suppressing the PI3K/AKT signaling pathway,suggesting its potential as a therapeutic agent for cervical cancer.