FTO regulates resistance of triple-negative breast cancer to adriamycin through Wnt/β-catenin signaling pathway
- VernacularTitle:FTO通过Wnt/β-catenin信号通路调节三阴性乳腺癌对阿霉素的耐药性
- Author:
Jin-min WU
1
;
Yu-hang QI
;
Jing-yi FANG
;
Wei-zhi MU
;
Zhao-lin CHEN
;
Zhao-yi YANG
Author Information
- Publication Type:Journal Article
- Keywords: FTO; triple-negative breast cancer; Wnt/β-catenin; adriamycin; drug resistance; apoptosis
- From: Chinese Pharmacological Bulletin 2025;41(12):2334-2341
- CountryChina
- Language:Chinese
- Abstract: Aim To explore the effect of FTO on adria-mycin resistance in triple-negative breast cancer through the Wnt/β-catenin signaling pathway and to reveal the underlying mechanism.Methods The MDA-MB-231/ADR drug-resistant cell line was constructed using a method of gradually increasing adriamycin concentra-tion with intermittent induction.The half-inhibitory concentration(IC50)of adriamycin for MDA-MB-231 and MDA-MB-231/ADR cells and the expression of FTO were compared.After knocking down FTO in MDA-MB-231/ADR cells,CCK-8,qRT-PCR,colony formation assay,transwell,flow cytometry,and Western blot were used to assess the changes in the IC50 of adri-amycin,cell proliferation,migration,invasion,apopto-sis,and the expression of related proteins.Results FTO was highly expressed in MDA-MB-231/ADR cells.After FTO knockdown,the IC50 value of adriamy-cin in MDA-MB-231/ADR cells decreased,and the a-bilities of proliferation,migration and invasion were weakened.In the FTO knockdown group,the expres-sion levels of Bax,cleaved-caspase3,GSK-3 β proteins and the apoptosis rate significantly increased,while the expression levels of Bcl-2,Wnt5a,β-catenin,c-myc,cyclin D1,and P-gp proteins decreased.Conclusion FTO may inhibit the apoptosis of MDA-MB-231/ADR cells through the Wnt/β-catenin signaling pathway,al-ter P-gp expression,and thereby enhance the resistance of MDA-MB-231/ADR cells to adriamycin.
