Effects of gypenosides mediated METTL3 regulation of m6A methylation on glycolysis in ovarian cancer cells
Objective To explore the effects of gypenosides(Gyp)on proliferation,apoptosis,and glycolysis of ovarian cancer cells,and exploring its impact on methyltransferase-like3(METTL3)mediated N6-methyladenosine(m6A)methylation in ovarian cancer and its mechanism of action.Methods The SKOV3 cells were divided into blank group(0.9%NaCl)and experimental-L,-M,-H groups(100,200 and 300 µg·mL-1 Gyp).The glucose consumption in cells were measured by kit.The expression levels of METTL3 mRNA were measured by quantitative real-time polymerase chain reaction(RT-qPCR).The apoptosis was determined by flow cytometry.Ovarian cancer model was constructed by subcutaneous injection of ovarian cancer SKOV 3 cell)in nude mice.After successful mold formation,10 mice were randomly divided into control group(0.9%NaCl)and experimental-L,-M,-H groups(50,100 and 150 mg·kg-1 Gyp),with 10 mice in each group.The RT-qPCR were used to detected the mRNA expression of glucose transporter 1(GLUT1)and hexokinase 2(HK2)in transplanted tumors.Results In SKOV3 cells,the glucose consumption of experimental-M,experimental-H and blank groups were(7.29±0.67),(6.15±0.22)and(15.69±0.70)μmol/1×105 cells;the relative expression levels of METTL3 mRNA were 0.47±0.01,0.30±0.01 and 1.02±0.01;the apoptosis rates were(13.52±0.50)%,(14.26±1.30)%and(3.50±0.78)%;the above indexes were statistically different between the experimental-M,-H groups and the blank group(all P<0.01).In ovarian cancer transplantation tumor in nude mice,the relative expression levels of GLUT1 mRNA in experimental-M,experimental-H and blank groups were 0.52±0.03,0.29±0.01 and 1.02±0.02;the relative expression levels of HK2 mRNA were 0.54±0.04,0.32±0.01 and 1.01±0.02;the differences of above indexes were statistically significant between the experimental-M,-H groups and the blank group(all P<0.01).Conclusion Gypenosides may exert anticancer effects in ovarian cancer by inhibiting glycolysis,which may be related to the inhibition of METTL3 mediated m6A methylation.