Role and mechanism of NHE1 inhibitor EIPA in hepatocellular carcino-ma cells
10.3969/j.issn.1000-4718.2025.03.002
- VernacularTitle:NHE1抑制剂EIPA在肝癌细胞中的作用及机制
- Author:
Hai JIN
1
;
Qian LIU
1
;
Jing LI
1
;
Shiyu ZHAO
1
;
Jiaxing ZHU
1
Author Information
1. 遵义医科大学附属医院消化病医院、遵义医科大学附属医院消化内科,贵州 遵义 563000
- Publication Type:Journal Article
- Keywords:
Na+/H+exchanger 1;
ethylisopropylamiloride;
hepatocellular carcinoma;
acidic tumor microenvi-ronment
- From:
Chinese Journal of Pathophysiology
2025;41(3):427-432
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effects of ethylisopropylamiloride(EIPA),an inhibitor of Na+/H+ex-changer 1(NHE1),on the proliferation,migration,invasion,cell cycle and apoptosis of hepatocellular carcinoma cells,and to explore its mechanisms.METHODS:The human hepatocellular carcinoma cell line Huh7 was cultured in vitro,and treated with different concentrations of EIPA.The mRNA and protein expression of NHE1 in Huh7 cells was assessed by RT-qPCR and Western blot.The proliferation of Huh7 cells was examined by kFluor488-EdU staining.The migration and invasion of Huh7 cells were assessed by Transwell assays.The cell cycle distribution and apoptosis of these cells were detected by flow cytometry.Moreover,the intracellular pH was measured via the PTI high-speed ion imaging system.RE-SULTS:Treatment with EIPA significantly suppressed the mRNA and protein expression of NHE1(P＜0.01).It signifi-cantly inhibited the proliferation,migration and invasion of Huh7 cells(P＜0.05 or P＜0.01),promoted their apoptosis(P＜0.01),and caused significant S-phase arrest(P＜0.01).It also significantly reduced the intracellular pH of Huh7 cells.CONCLUSION:The NHE1 inhibitor EIPA regulates the intracellular pH by inhibiting the expression and function of NHE1,which consequently affects the proliferation,migration,invasion,cell cycle,and apoptosis of Huh7 cells.There-fore,NHE1 may be a potential target for the treatment of hepatocellular carcinoma.
