Role of PI3K/Akt Pathway in MMC Induced Apoptosis of Liver Stem Cells
10.3870/j.issn.1672-0741.2017.01.015
- VernacularTitle:PI3K/Akt途径在MMC诱导的肝干细胞凋亡中的作用
- Author:
Huijie LIU
;
Dan XU
;
Rong PENG
- Keywords:
hepatic stem cell;
apoptosis;
mitomycin;
PI3K;
Akt;
signal pathway
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2017;46(1):68-71
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of PI3K/Akt pathway in mitomycin(MMC) induced apoptosis of liver stem cells.Methods Rat liver stem ceils were stimulated with MMC,and the effect of MMC on the apoptosis rate of WB-F334 cells at different time points(6,12,24 h),as well as the effects of different concentrations of (0.2,0.4,0.6,0.8,1.0 mg/mL) MMC on the cytotoxicity of WB-F334 cells were evaluated;moreover,cells were treated with p38 MAPK inhibitor and PI3K/Akt inhibitor,and the roles of MAPK and PI3K/Akt signaling pathway in MMC mediated apoptosis of WB-F334 cells were explored.Results The apoptosis rate of the MMC-treated WB-F334 increased with time(P<0.05).Compared with the un-treated control group,different concentrations of MMC had obvious cytotoxicity on liver stem cells,and the cytotoxicity increased with concentration.Western blotting results showed that Akt and MAPK in WB-F334 cells were significantly phosphorylated 15 min after MMC stimulation;the degree of phosphorylation decreased with time,and phosphorylation disappeared after 60 min,suggesting that the p38 MAPK,PI3K/Akt pathway can be activated by MMC;furthermore,when p38 MAPK inhibitor was added to MMC treated cells,the apoptosis rate of p38 MAPK inhibitor treated cells showed no significant difference compared to the un-treated cells(P>0.05),indicating that the MAPK pathway had no significant effect on MMC induced WP,-F334 cell death;however,when the PI3K/Akt inhibitor(API-2)was added,the apoptosis rate of API-2 treated cells was significantlv decreased compared to the un-treated cells(P<0.05),indicating that the PI3K/Akt pathway had a significant effect on MMC induced apoptosis of WB-F334 cells(P<0.05).Conclusion Stimulation of MMC can induce apoptosis of hepatic stem cells WB-F334 through the activation of the PI3K/Akt signaling pathway.