Effects of simvastatin on PI3K/AKT signaling pathway in human acute monocytic leukemia cell line SHI-1.
- Author:
Mei ZENG
1
;
Wei-Ying GU
;
Ting-Xiu JIANG
;
Zi-Xing CHEN
;
Guo-Qiang QIU
;
Man LI
;
Hao-Qing WU
;
Zhi-Lin WANG
;
Xiao-Bao XIE
;
Xiang-Shan CAO
Author Information
1. Department of Hematology, Third Affiliated Hospital of Suzhou University, Changzhou, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Down-Regulation;
Gene Expression Regulation, Leukemic;
Humans;
Leukemia, Monocytic, Acute;
metabolism;
Phosphatidylinositol 3-Kinases;
metabolism;
Proto-Oncogene Proteins c-akt;
metabolism;
Signal Transduction;
drug effects;
Simvastatin;
pharmacology
- From:
Journal of Experimental Hematology
2012;20(2):268-272
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin (SV) on proliferation, apoptosis and the PI3K/AKT signaling pathway in human acute monocytic leukemia cell line SHI-1. SHI-1 cells were incubated with different concentrations of SV (5, 10, 15 µmol/L). Otherwise, SHI-1 cells without any treatment were used as control. Cells in different groups were collected at 24, 48 and 72 h after incubation for further detection. MTT method was used to assay the growth inhibition rate and flow cytometry was used to detect the early stage apoptosis ratio. The human PI3K-AKT Signaling Pathway RT(2) Profiler(TM) PCR Array was used to detect the expression of 84 genes involved in PI3K-AKT signaling. The results indicated that the SV inhibited the proliferation and inducted the apoptosis of SHI-1 cells in time- and dose-dependent manners significantly. The growth inhibition rates of SHI-1 cells treated with 15 µmol/L SV for 24, 48 and 72 h were 26.82, 47.09 and 63.92, respectively; and their early stage apoptosis ratios were 5.75, 13.25 and 15.59, respectively. Compared with the control group, expression levels of 39 genes were changed in the group of 15 µmol/L SV at 48 h, among them 26 genes were down-regulated and 13 genes were up-regulated. It is concluded that the SV can inhibit proliferation and induce apoptosis of SHI-1 cells, and the mechanism may be associated with the changes of gene expression level in PI3K-AKT signaling pathway regulated by SV.
