Influence of troglitazone on proliferation of human liver cancer cell line HepG2 in vitro and on β-catenin signaling pathway
10.3724/SP.J.1008.2008.00011
- Author:
Yan-Ming ZHOU
1
Author Information
1. Department of Hepato-Biliary-Pancreato-Vascular Surgery
- Publication Type:Journal Article
- Keywords:
β-catenin;
Liver neoplasms;
Peroxisome proliferator-activated receptor;
Troglitazone
- From:
Academic Journal of Second Military Medical University
2010;29(1):11-14
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the influence of troglitazone, a potent peroxisome proliferator-activated receptor (PPAR) gamma agonist, on proliferation and β-catenin signaling pathway of human liver cancer cell line HepG2 in vitro, and to discuss its possible anti-cancer mechanism. Methods: HepG2 cells were cultured in vitro and the cell growth was assessed by MTT assay after exposure to different concentrations of troglitazone (5, 10, 20, 40, 80 and 100 μmol/L) for 120 h, and the results were compared with that of the control cells (cultured normally). Flow cytometry was used to assess cell cycle of HepG2 cells treated with troglitazone at 10 μmol/L and of normal control cells. The subcellular location of β-catenin was investigated by immunocytochemistry in troglitazone (10 μmol/L)-treated and control cells. Expression of cyclin D1 and c-myc proteins was examined by Western blotting assay. Results: MTT assay demonstrated that, after treatment with 5, 10, 20, 40, 80 and 100 μmol/L of troglitazone, the cell survival rates were (96.8±1.2)%, (53.4±1.2)%, (42.3±1.2)%, (31.4±1.0)%, (13.6± 0.8)% and (9.6±0.7)%, respectively. Compared with control cells, cells treated with 10 μmol/ L troglitazone showed an increased proportion of cells at the G0/G1 phase ([67.6±0.5]% vs [56.3±1.5]%, P<0.01) and decreased proportion of cells at the S phase ([20.6±0.5]% vs [25±1.0]%, P<0. 01). β-catenin was located in the nucleus of the control cells and in the cytoplasm of the troglitazone-treated cells. Western blotting analysis showed that the expression of c-myc and cyclin D1 proteins in troglitazone-treated cells was lower than that in the control cells. Conclusion: Troglitazone can inhibit the proliferation of HepG2 cells in a dose-dependent manner, which may be associated with regulation of the β-catenin signaling pathway and inhibition of target protein expression.
