Effects of loganin on the biological behavior of cervical cancer cells mediated by glutamine metabolism via regulation of the NFE2L2-FTH1-GPX4 pathway
10.12007/j.issn.0258-4646.2025.07.002
- VernacularTitle:马钱苷通过调控NFE2L2-FTH1-GPX4影响谷氨酰胺代谢介导的宫颈癌细胞生物学行为
- Author:
Yan LEI
1
;
Chun FENG
1
;
Qian ZOU
1
;
Yi DONG
1
;
Hongmei LIAN
1
;
Xin DU
1
Author Information
1. 湖北省妇幼保健院妇科,武汉 430070
- Publication Type:Journal Article
- Keywords:
loganin;
nuclear factor red blood cell 2 related factor 2;
ferritin heavy chain 1;
glutathione peroxidase 4;
glutamine metabo-lism;
cervical cancer
- From:
Journal of China Medical University
2025;54(7):583-589
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of loganin(Log)on glutamine metabolism in cervical cancer through the regula-tion of nuclear factor red blood cell 2 related factor 2(NFE2L2)-ferritin heavy chain 1(FTH1)-glutathione peroxidase 4(GPX4).Methods Bioinformatics analysis was conducted to identify common targets of Log,glutamine metabolism,and cervical cancer.Hela cells were divided into Blank,control(Ctrl),Log,cisplatin(DDP),NFE2L2 activator(TBHQ),NFE2L2 inhibitor(ML385),and TBHQ+Log groups to detect cell proliferation,invasion,apoptosis,glutamine metabolism,and the protein expression of NFE2L2,FTH1,and GPX4.A cervical cancer xenograft mouse model was established to investigate the in vivo effects of Log on the progression of cervical cancer.Results Bioinformatics analysis confirmed that NFE2L2 might be a target of Log in the treatment of cervical cancer.Both Log and DDP reduced the proliferation and invasion abilities of Hela cells,increased apoptosis,and decreased the levels of glutamine and glutamic acid,as well as the protein expression of glutaminase(GLS1)and glutamic dehydrogenase(GLUD1,P<0.05).The NFE2L2 activator TBHQ had opposite effects,whereas ML385 had a similar impact on the Log.Additionally,Log treatment inhibited the protein expression of NFE2L2,FTH1,and GPX4(P<0.05).Animal experiments showed that Log significantly inhibited cervical cancer progression(P<0.05).Conclusion Log affects cervical cancer progression via glutamine metabolism by inhibiting the NFE2L2-FTH1-GPX4 signaling pathway.