Impacts of remifentanil on the proliferation,migration,and invasion of liver cancer cells by regulating SPHK1/S1P/S1PR3 signaling pathway
10.3969/j.issn.1009-9905.2025.09.002
- VernacularTitle:瑞马唑仑调节SPHK1/S1P/S1PR3信号通路对肝癌细胞增殖和迁移及侵袭的影响
- Author:
Ai-bei MA
1
;
Yan-ru LI
;
Shao-xia QI
;
Bing-lun SUN
Author Information
1. 河北省沧州中西医结合医院 麻醉科(河北 沧州 160001)
- Publication Type:Journal Article
- Keywords:
Remimazolam;
Sphingosine kinase 1/sphingosine 1-phosphate/sphingosine 1-phosphate receptor 3 signaling pathway;
Hepatocellular carcinoma cells;
Proliferation;
Migration;
Invasion
- From:
Chinese Journal of Current Advances in General Surgery
2025;28(9):680-685
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the impacts of remimazolam(REM)on the proliferation,migration,and invasion of hepatocellular carcinoma cells by regulating sphingosine kinase 1/sphingosine 1-phosphate/sphingosine 1-phosphate receptor 3(SPHK1/S1P/S1PR3)signaling pathway.Methods:Human hepatocellular carcinoma cell line HepG2 was treated with REM at concentrations of 0,20,40,80,160,and 320 μmol/L respectively.Cell survival rate was measured,and drug concentrations were screened.Based on the results of cell survival rate,the logarithmic phase cells were di-vided into five groups:Control group,low,medium,and high concentrations of remifentanil groups(REM-L,REM-M,REM-H groups;20,40 and 80 μmol/L),and high concentrations of remifentanil+SPHK1 activator group(REM-H+K6PC-5 group).MTT assay was used to detect the survival rate of HepG2 cells.Plate cloning experiment was performed to de-tect cell proliferation ability.Scratch experiment was performed to detect cell migration ability.Transwell chamber method was performed to detect cell invasion ability.Flow cytometry was used to detect cell apoptosis.Western blot was used to detect the SPHK1,S1P,S1PR3,Bax,and Bcl-2 proteins in cells.Results:For the Control group,the REM-L,REM-M,and REM-H groups showed that the number of HepG2 cell clones,scratch healing rate,invasion rate,Bcl-2,SPHK1,S1P,S1PR3,and N-cadherin proteins gradually decreased with increasing REM concentration,while the apoptosis rate and Bax,E-cadherin proteins showed an opposite trend(P<0.05).For the REM-H group,the REM-H+K6PC-5 group showed a clear increase in the number of HepG2 cell clones,scratch healing rate,invasion rate,Bcl-2,SPHK1,S1P,S1PR3,and N-cadherin proteins,and a clear decrease in the apoptosis rate and Bax,E-cadherin proteins(P<0.05).Conclusion:REM may inhibit the proliferation,migration,and invasion of hepatocellular carcinoma cells and promote cell apoptosis by suppressing SPHK1/S1P/S1PR3 signaling pathway.