KIF2A Strengthens the Chemoresistance of Hepatocellular Carcinoma Cells Against 5-FU Through Notch1/Hes1Pathway
10.11969/j.issn.1673-548X.2025.01.014
- VernacularTitle:KIF2A通过Notch1/Hes1途径增强肝癌细胞对5-FU的化疗耐药性
- Author:
Qi WU
1
;
Ye JIN
1
;
Zhi CHEN
1
Author Information
1. 310012 杭州,浙江省立同德医院普外科
- Publication Type:Journal Article
- Keywords:
KIF2A;
Liver cancer;
Chemotherapy resistance;
Notch1/Hes1
- From:
Journal of Medical Research
2025;54(1):73-78
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the impact of kinesin family member 2A(KIF2A)on the resistance of hepatocellular carcinoma cells to 5-FU and its underlying mechanism.Methods The drug resistance of hepatocellular carcinoma cell line BEL7402 to 5-FU was induced through an increasing concentration gradient combined with high-dose intermittent shock to construct a drug-resistant strain,BEL7402/5-FU.KIF2A-silenced BEL7402/5-FU cells were then built using the lentivirus technique.Valproic acid(VPA),an agonist of the Notch1/Hes1signaling pathway,was employed to treat the KIF2A-silenced BEL7402/5-FU cells.The cell viability,apoptosis rate,and protein expressions of KIF2A,cleaved-caspase-3,Notch1,and Hes1 were detected by CCK-8 assay,western blot,immunofluorescence,and flow cytometry,respectively.Results The BEL7402/5-FU cells exhibited strong resistance to 5-FU,with an IC50 value of 344.2μmol/L,which was 92 times that of the BEL7402 cells(IC50=3.730μmol/L).Compared to the BEL7402 cells,the expression of the KIF2A protein in the BEL7402/5-FU cells was significantly increased(P＜0.001).Compared with the si-NC group,the viability of the BEL7402/5-FU cells in the si-KIF2A group was significantly decreased(P＜0.001).At the same time,the apoptosis rate and the expression of the cleaved-caspase-3 protein were significantly increased(P＜0.001),and the expressions of Notch1 and Hes1 protein were significantly decreased(P＜0.001).Compared with the si-NC+5-FU group,the activity of BEL7402/5-FU cells in the si-KIF2A+5-FU group was significantly decreased(P＜0.001)and the apoptosis rate was significantly increased(P＜0.001).Compared with the si-KIF2A+5-FU group,the activity of BEL7402/5-FU cells in the si-KIF2A+5-FU+VPA group was significantly increased(P＜0.001),the apoptosis rate was significantly decreased(P＜0.001),and the expressions of Notch1 and Hes1 proteins were significantly increased(P＜0.001).Conclusion Silencing KIF2A reduces the drug resistance of BEL7402/5-FU cells to 5-FU by inhibiting the activity of the Notch1/Hes1signaling pathway.
