Induction effect of TTF1-NP on human hepatoma cell apoptosis through ERS-mediated pathway
10.13481/j.1671-587x.20150604
- VernacularTitle:TTF1-NP 诱导人肝癌 HepG-2细胞凋亡的内质网应激作用
- Author:
Bin XIAO
;
Rongrong LIU
;
Bingtong LIU
;
Xuewu ZHANG
- Publication Type:Journal Article
- Keywords:
5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone nanoparticles;
endoplasmic reticulum stress;
apoptosis;
liver neoplasms
- From:
Journal of Jilin University(Medicine Edition)
2015;(6):1118-1123
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of different doses of 5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone nanoparticles (TTF1-NP)on the apoptosis of human hepatoma cells and human normal hepatocytes,and to explore their mechanisms through endoplasmic reticulum stress (ERS)-meditated apoptosis pathway. Methods The human hepatoma cell lines (HepG2,Hep3B and PLC/PRF/5)and human hepatocytes (Chang Liver)were used as cell model, and divided into vehicle, 5-Fu and TTF1-NP treated groups with the concentrations of 50, 100 and 200 μmol·L-1 respectively. The inhibitory effects of TTF1-NP on the cell growth were assessed using MTT assay and the best inhibitory one (HepG-2)was selected as the main research cell lines.Flow cytometry was used to detect the TTF1-NP-induced apoptosis;Western blotting and immunocytochemistry were used to determine the expressions of ERS key proteins.Finally,the expressions of key proteins were detected by Western blotting after using the ERS inhibitor 4-PBA.Results Compared with vehicle group,the inhibitory rates of growth of 4 kinds of human hepatoma cells in different concentrations of TTF1-NP groups were increased (P <0.05 or P <0.01);moreover,the inhibitory effects of TTF1-NP were in a time-and dose-dependent manner.Compared with vehicle group,the apoptotic rates of the cells in TTF1-NP groups were increased in a dose-dependent manner (P <0.05 or P < 0.01 );the expression levels of ERS key proteins GRP78 and caspase-4 were increased with the increasing of the concentration of TTF1-NP (P < 0.05 or P < 0.01).The expression levels of ERS key proteins GRP78 and caspase-4 induced by TTF1-NP were inhibited by ERS inhibitor 4-PBA (P < 0.05 or P < 0.01 ). Conclusion TTF1-NP can induce the apoptosis of HepG2 cells;ERS pathway plays a central role in TTF1-NP-induced apoptosis of HepG-2 cells.
