Effects of gypenosides mediated METTL3 regulation of m6A methylation on glycolysis in ovarian cancer cells
10.13699/j.cnki.1001-6821.2024.22.010
- VernacularTitle:绞股蓝总苷介导METTL3调控m6A甲基化对卵巢癌细胞糖酵解的影响
- Author:
Hao GAO
1
;
Jiao ZHAO
;
Wei-yan CHEN
;
Tian-min JI
;
Qun WANG
;
Yuan CAO
Author Information
1. 辽宁中医药大学研究生学院,辽宁沈阳 110847
- Publication Type:Journal Article
- Keywords:
gypenosides;
ovarian cancer;
glycolysis;
methyltransferase 3;
N6-methyladenosinem methylation
- From:
The Chinese Journal of Clinical Pharmacology
2024;40(22):3264-3269
- CountryChina
- Language:Chinese
-
Abstract:
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.
