Effects of simvastatin on the proliferation of tumor cells in vitro
10.3321/j.issn:0253-3766.2008.01.006
- VernacularTitle:辛伐他汀抑制肿瘤细胞增殖及其可能的机制
- Author:
Gui-Fen SHEN
1
;
Jian-Gang JIANG
;
Shao-Xian HU
;
Dao-Wen WANG
Author Information
1. 华中科技大学同济医学院附属同济医院
- Keywords:
Simvastatin;
Signal transduction pathway;
Tumor cells proliferation
- From:
Chinese Journal of Oncology
2008;30(1):21-25
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the antiproliferative effect of simvastatin on tumor cells and its mechanism. Methods Tumor cells U87, Hela, HCT-116 (p53+/+), HCT-116 (p53-/-) were incubated with simvastatin at different concentrations, and with 100 μmol/L simvastatin for 24 h ,48 h ,72 h and 96 h. Cell proliferation was determined by MTT. U87, HCT-116(p53 +/+ ), HCT-116(p53 -/- ) cells were incubated with simvastatin for 48 hours, and the cell cycle distributions were analyzed by flow cytometry. The levels of total p21 protein synthesis and phosphorylation of ERK1/2, p38, JNK and Akt were determined by Western blot. Results The cell growth of all the four types of tumor cells U87, Hela, HCT- 116(p53+/+) and HCT-116(p53 -/- ) was suppressed in a dose- and time-dependent manner (P< 0.05). In addition, incubation with simvastatin arrested cells at G1 phase of the cell cycle accompanied by up-regulation of cell cycle inhibitor p21. Western blot analysis showed that simvastatin markedly increased the phosphorylation of p38 and JNK in the cells, but activities of protein kinases ERK1/2 and Akt in the intracellular signal transduction pathway remained unchanged. Conclusion Those observations suggest that statins can inhibit the proliferation of tumor cells beyond their cholesterol-lowing effect and p21, p38 and JNK may play an important role in simvastatin-induced proliferation inhibition.
