Study on the inhibitory effect of 18β-glycyrrhetinic acid combined with 5-Fu on Lewis lung carcinoma cells

Tian Qihui; Liu Yali; Yang Mingxuan; Long Yali; Zhang Yong

doi:10.20154/j.cnki.issn1672-9692.2025.06.005

Abstract：The experiment aims to investigate the inhibitory effect of 18β-glycyrrhetinic acid(GLA),a component of licorice,combined with 5-fluorouracil(5-Fu),on Lewis lung carcinoma cells based on the glyoxalase 1(GLO1)metabolic pathway,providing a reference for the clinical treatment of lung cancer in small animals.The experiment adopted the in vitro culture of Lewis lung carcinoma cells and used the cells that had grown to the logarithmic growth phase for the experiment.The experiment was set up with Control group,5-Fu group,GLA group,and 5-Fu+GLA group.Cells of each group were spread in 96-well plates,after overnight adhesion,Contro group was routinely cultured.In each experimental group,0.5 mg/L 5-Fu(5-Fu group),50 μmol/L GLA(GLA group),and 0.5 mg/L 5-Fu+50 μmol/L GLA(5-Fu+GLA group)were added respectively,with five duplicate wells in each group.The proliferation rate and apoptosis rate of Lewis lung carcinoma cells in each group were detected by CCK8 method and flow cytometry in the experiment.The relative expression levels of metabolites methylglyoxal and D-lactic acid were detected by ELISA.The fluorescence expression level of GLO1 protein was detected by immunofluorescence method.The results showed that the cell morphology in Control group was more regular and the size was relatively uniform.After the intervention of GLA or in combination with 5-Fu,the cells became round and brighter,and shrank.Compared with Control group,the cell proliferation rate in GLA group was significantly decreased(P<0.05),and the cell proliferation rates in 5-Fu group and 5-Fu+GLA group were extremely decreased(P<0.01).Compared with Control group,the relative expression levels of methylglyoxal in cells was extremely increased after GLA intervention(P<0.01),and the relative expression levels of D-lactic acid was extremely decreased(P<0.01).The relative expression levels of methylglyoxal in the cells of 5-Fu group increased significantly(P<0.05).Compared with 5-Fu group,the relative expression levels of methylglyoxal in the cells of 5-Fu+GLA group was significantly increased(P<0.05),and the relative expression levels of D-lactic acid was extremely decreased(P<0.01).Compared with Control group,the fluorescence expression level of GLO1 protein in cells decreased significantly after GLA intervention,while there was no significant change in 5-Fu group.The fluorescence expression level of GLO1 protein in cells decreased most significantly after combined GLA intervention.Studies have shown that GLA can inhibit the activity of GLO1 enzyme and promote the inhibitory effect of 5-Fu on Lewis lung carcinoma cells.