Effects of Met combined with GAD on proliferation and apoptosis of human endometrial cancer cells

LONG Yun; LIU Weijie; FU Hairong; PANG Yi; YUAN Yunchuan

doi:10.3969/j.issn.1002-266X.2025.08.002

Abstract：Objective To explore the effects and mechanisms of metformin(Met)in combination with ganoderic ac-id D(GAD)on the proliferation and apoptosis of human endometrial cancer cells(Ishikawa cells).Methods Ishikawa cells in the logarithmic growth phase were divided into four groups:the Control group,the Met group(8 mmol/L Met),the GAD group(10 μg/mL GAD),and the combined group(8 mmol/L Met and 10 μg/mL GAD).Cell proliferation and apoptosis were respectively evaluated by EdU staining and Annexin V-FITC/PI staining following Met and GAD alone or their combination treatments for 24 h.Glucose transporter 3(GLUT3)that mediated glucose uptake was detected by immu-nofluorescence(IF).Glucose uptake was measured by using 2-deoxyglucose analog(2-NBDG).The expression of glycoly-sis-related proteins[hexokinase 2(HK2),lactate dehydrogenase A(LDHA)]in Ishikawa cells was detected by Western blotting.Results Compared with the Control group,the cell proliferation rates were lower,the apoptosis rates were high-er,the 2-NBDG uptake of cells was less,and the expression levels of GLUT3,HK2 and LDHA proteins in Ishikawa cells were lower in the Met group,the GAD group,and the combined group(all P<0.05).Compared with the Met group and the GAD group,the Met+GAD group showed a lower cell proliferation rate,a higher apoptosis rate,a reduced cellular uptake of 2-NBDG,and lower relative expression levels of GLUT3,HK2,and LDHA proteins(all P<0.05).Conclusion Metfor-min can synergize with GAD to inhibit the proliferation of Ishikawa cells and promote their apoptosis,and its mechanism of action may be related to the inhibition of glucose uptake and glycolysis in Ishikawa cells,thereby reducing energy supply.