Objective To reveal the role of Phosphatidylinositol 3-kinases (PI3Ks) in regulating human diploid fibroblast (2BS cell) senescence as well as the possible mechanisms involved.Methods Using a PI3Ks specific inhibitor,...Objective To reveal the role of Phosphatidylinositol 3-kinases (PI3Ks) in regulating human diploid fibroblast (2BS cell) senescence as well as the possible mechanisms involved.Methods Using a PI3Ks specific inhibitor, LY294002, cell cycle, apoptosis, proliferation, senescence association β-galactosidase staining as well as senescence association CKIs, p16INK4 and p21Cip1 protein expressions were all measured in the low passages of 2BS cells.Results Both 25 μmol/L and 50 μmol/L concentrations of LY294002 could cause a significant decrease in cells entering into S phase, and this cell cycle of G, phase arrest was dose-dependent. Meanwhile, LY294002 contributed to apoptosis, caused 2BS cell growth arrest, and activated senescence association p-galactosidase (P<0. 05). In addition, LY294002 could induce time-course expressions of p16INK4 and p21Cip1 in 2BS cell lines.Conclusions PI3Ks inhibitor LY294002 could induce senescence-like changes in 2BS cell lines. Two senescence associated CKIs, p16INK4 and p21Cip1, might be involved in this senescence phenotype proceeding in 2BS cell lines.展开更多
基金This work was supported by the National Science Foundation of China(No.G399301070)and the Major State Basic Research Development Program of China(No.G200057001 and G1999053906).
文摘Objective To reveal the role of Phosphatidylinositol 3-kinases (PI3Ks) in regulating human diploid fibroblast (2BS cell) senescence as well as the possible mechanisms involved.Methods Using a PI3Ks specific inhibitor, LY294002, cell cycle, apoptosis, proliferation, senescence association β-galactosidase staining as well as senescence association CKIs, p16INK4 and p21Cip1 protein expressions were all measured in the low passages of 2BS cells.Results Both 25 μmol/L and 50 μmol/L concentrations of LY294002 could cause a significant decrease in cells entering into S phase, and this cell cycle of G, phase arrest was dose-dependent. Meanwhile, LY294002 contributed to apoptosis, caused 2BS cell growth arrest, and activated senescence association p-galactosidase (P<0. 05). In addition, LY294002 could induce time-course expressions of p16INK4 and p21Cip1 in 2BS cell lines.Conclusions PI3Ks inhibitor LY294002 could induce senescence-like changes in 2BS cell lines. Two senescence associated CKIs, p16INK4 and p21Cip1, might be involved in this senescence phenotype proceeding in 2BS cell lines.
