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 p2 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. LY294002 contributed to apoptosis, caused 2BS cell growth arrest, and activated senescence association p-galactosidase (P <0.05). 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 CK Is, p16INK4 and p2