Effect of phosphatidylinositol-3 kinase inhibitor on 17β-estradiol-induced proliferation and apoptosis in Ishikawa and HEC-1A cells

Aim: to observe the influence of PI3K inhibitor (LY294002) on proliferation, cell cycle progression, and apoptosis in endometrial carcinoma cells stimulated by E2 and to explore the preliminary possible effect of LY294002 on treating endometrial carcinoma. Methods:The effects of LY294002 on E2-induced proliferation, apoptosis, and cell cycle distrubution of endometrial cancer cells were detected by monotetrazolium (MTT) assay and fluorescence-activated cell sorting technique. Results: With increased concentrations of E2, the A(570 nm) values of endometrial cancer cells increased gradually especially in Ishikawa in a time-dependent manner(F=3.915,P=0.043). Cell cycle distribution analysis revealed that percentage of Ishikawa cells at G0-G1 phase(F=50.926, P≤0.001) decreased and percentage of S phase cells(F=17.836, P=0.001) increased significantly, whereas that of HEC-1A cell didn't show significant alteration. Cotreatment of endometrial cancer cells with LY294002, A(570 nm) values of both cells decreased also showing a time-dependent manner(F=10.398,P=0.001; F=5.542,P=0.043), the percentage of apoptotic cells increased significantly (P0.001), the percentage of the cell population at G0-G1 phase (F=32.024, P≤0.005; F=14.725,P≤0.017)increased and the percentage of cancer cells at S (F=30.132, P≤0.001; F=24.72,P≤0.01)phase decreased.Conclusion: Inhibition of PI3K activity by LY294002 could inhibit endometrial cancer cells' proliferation induced by E2 and induce the G1 cell cycle arrest and cell apoptosis. PI3K/Akt pathway presents an appealing therapeutic target on endometrial cancer.