Levels of P27Kip1 expression and apoptosis in HL-60 cells after treatment with TGF-ß1 and/or arsenic trioxide.
- Author:
Jin-Xiang YU
1
;
Yan-Li MENG
;
Yan LI
Author Information
1. Department of Hematology, China Medical University First Clinical Hospital, Shenyang 110001, Liaoning Province, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Arsenicals;
pharmacology;
Cyclin E;
metabolism;
Cyclin-Dependent Kinase Inhibitor p27;
metabolism;
Gene Expression Regulation, Leukemic;
HL-60 Cells;
Humans;
Oxides;
pharmacology;
Proto-Oncogene Proteins c-bcl-2;
metabolism;
Transforming Growth Factor beta1;
pharmacology
- From:
Journal of Experimental Hematology
2010;18(4):893-897
- CountryChina
- Language:Chinese
-
Abstract:
This study was purposed to investigate the effects of TGF-beta1 and arsenic trioxide (As₂O₃) on cell apoptosis, cell cycle and changes of P27(Kip1), endogenous TGF-ß1, cyclin E and BCL-2 in HL-60 cells, and to explore the relationship between expression of P27(Kip1) and apoptosis induced by As₂O₃ and/or TGFß1. Cell apoptosis and cell cycle changes of HL-60 cells treated with As₂O₃ and/or TGFß1 were detected by cytomorphologic observation and flow cytometry, the protein expressions of P27(Kip1), TGF-ß1, cyclin E and BCL-2 were measured by immunohistochemistry. The results showed the effect of 5 μmol/L of As₂O₃ was the most strong among the different concentration of As₂O₃ ,and the effect on apoptosis at 48 hour was more strong than that at 24 hours (p < 0.05). The TGF-beta1 (5 ng/ml) induced arrest of cells in G₁ phase (p < 0.05) compared with As₂O₃ alone and As₂O₃ combined with TGF-ß1, while there was no difference with control. P27(Kip1) expression was up regulated (p < 0.05), cyclin E and BCL-2 expression was down-regulated (p < 0.05) in TGFß1-treated group. BCl-2 expression was down regulated, endogenesis TGFß1 expression was up regulated (p < 0.05), and the level of P27(kip1) and cyclin E were not changed in As₂O₃-treated group (p > 0.05). The down-regulating effect of TGF-ß1 combined with As₂O₃ on BCL-2 protein was more strong than that in single factor treated group (p < 0.05). It is concluded that TGFß1 induces cell cycle arrest and apoptosis in HL-60 cells, while the P27(kip1) expression is up regulated. P27 protein is the key effector of TGFß-induced cell cycle arrest. The effect of TGF-ß1 combined with As₂O₃ on apoptosis as well as the down-regulation of BCL-2 protein in HL-60 cells is more strong than that in single factor-treated groups, that indicates the passages linking up each other.
