Phosphatidylinositol 3-kinase inhibitor, LY294002, induced senescence-like changes in human diploid fibroblasts.
- Author:
Shuping LI
1
;
Zongyu ZHANG
;
Tanjun TONG
Author Information
- Publication Type:Journal Article
- MeSH: Cells, Cultured; Cellular Senescence; drug effects; Chromones; pharmacology; Cyclin-Dependent Kinase Inhibitor p16; analysis; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; analysis; Dose-Response Relationship, Drug; Enzyme Inhibitors; pharmacology; Fibroblasts; drug effects; physiology; G1 Phase; drug effects; Humans; Morpholines; pharmacology; Phosphatidylinositol 3-Kinases; antagonists & inhibitors
- From: Chinese Medical Journal 2003;116(6):901-905
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo reveal the role of Phosphatidylinositol 3-kinases (PI3Ks) in regulating human diploid fibroblast (2BS cell) senescence as well as the possible mechanisms involved.
METHODSUsing a PI3Ks specific inhibitor, LY294002, cell cycle, apoptosis, proliferation, senescence association beta-galactosidase staining as well as senescence association CKIs, p16(INK4) and p21(Cip1) protein expressions were all measured in the low passages of 2BS cells.
RESULTSBoth 25 micro mol/L and 50 micro mol/L concentrations of LY294002 could cause a significant decrease in cells entering into S phase, and this cell cycle of G(1) phase arrest was dose-dependent. Meanwhile, LY294002 contributed to apoptosis, caused 2BS cell growth arrest, and activated senescence association beta-galactosidase (P < 0.05). In addition, LY294002 could induce time-course expressions of p16(INK4) and p21(Cip1) in 2BS cell lines.
CONCLUSIONSPI3Ks inhibitor LY294002 could induce senescence-like changes in 2BS cell lines. Two senescence associated CKIs, p16(INK4) and p21(Cip1), might be involved in this senescence phenotype proceeding in 2BS cell lines.
