2-Fluorofucose Increases Chemosensitivity of Human Breast Cancer Cells to Paclitaxel
10.13865/j.cnki.cjbmb.2025.02.1264
- VernacularTitle:2-氟岩藻糖增加人乳腺癌细胞紫杉醇化疗敏感性作用研究
- Author:
Bo FENG
1
;
Ya-Jie CUI
;
Wen-Bin ZHU
;
Xiu-Li GAO
;
Li-Ling YUE
Author Information
1. 齐齐哈尔医学院教务处,黑龙江 齐齐哈尔 161006
- Publication Type:Journal Article
- Keywords:
breast cancer(BC);
fucosylation;
2-fluoro-fucose;
drug resistance;
chemotherapy sensitivity
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(4):597-606
- CountryChina
- Language:Chinese
-
Abstract:
Paclitaxel(PTX)is a first-line chemotherapy drug for breast cancer,but its resistance issues significantly impact clinical treatment efficacy.Fucosylation,especially core fucosylation,is closely related to tumor chemoresistance,resulting in poor chemotherapy responses and poor prognosis in patients.In this study,we investigated the effect and mechanism of the fucosylation inhibitor 2-fluorofucose(2-F-Fuc)on the chemosensitivity of paclitaxel-resistant breast cancer MCF-7/PTX cells.The drug resistanceindex(RI)of MCF-7/PTX cells was 8.49 by MTT assays.Western blotting,real-time PCR,enzyme-linked immu-nosorbent assay(ELISA)and Lens Culinaris Agglutinin(LCA)lectin imprinting showed that compared with MCF-7 cells,the expression of FUT8,MDR1and core fucosylation in MCF-7/PTX cells was high.Western blotting showed that 2-F-Fuc had a significant inhibitory effect on the growth of MCF-7/PTX cells,and the expression levels of FUT8 and MDR1 were significantly down-regulated after 2-F-Fuc treatment,and the down-regulation was more pronounced in the PTX and 2-F-Fuc combination group(P<0.05).Compared to the control,expression of PCNA in MCF-7/PTX cells in the PTX and the 2-F-Fuc group were down-regulated,and the apoptosis-related proteins,such as cleaved caspase-3 and Bax/Bcl-2 were in-creased.The level of p-PI3K and p-AKT were down-regulated,and the changes in the combination of 2-F-Fuc and PTX were more robust(P<0.05).The above results showed that the core fucosylation level of MCF-7/PTX cells was significantly increased,and 2-F-Fuc could reduce the core fucosylation level of MCF-7/PTX cells by inhibiting the expression of FUT8,and enhance the sensitivity of drug-resistant cells to PTX,which may correlate with the downregulation of PI3K/AKT signaling pathway proteins.