Phosphatidylinositol 3-Kinase Inhibitor LY294002 Suppresses Proliferation and Sensitizes Doxorubicin Chemotherapy in Bladder Cancer Cells

Background: Phosphatidylinositol 3-kinase (PI3K)-AKT signaling is a well-characterized pathway involved in control of cell proliferation, apoptosis and oncogenesis. LY294002 is a commonly used pharmacologic inhibitor which acts at the ATP-binding site of the PI3K enzyme, and thus selectively inhibits the PI3K-AKT nexus. The purpose of the study was to examine whether PI3K inhibited by LY294002 had effects in human bladder cancer cells. Methods: After treatment with LY294002, MTT assay, a chemosensitivity test, colony formation assay, apoptosis assay and Western blot analysis were conducted in EJ cells. Result: EJ cells treated with LY294002 showed significant AKT phosphorylation suppressing in a dose-response manner. Additionally, the PI3K/AKT signaling inhibitor LY294002 suppressed cell proliferation and enhanced chemosensitivity to doxorubicin in human bladder cancer EJ cells. Furthermore, LY294002 increased cell apoptosis to doxorubicin. Conclusion: The augmentation of doxorubicin with the PI3K inhibitor LY294002 may resolve the multidrug resistance of bladder cancer, and this may be a new strategy for achieving tolerance for chemotherapeutic agents in bladder cancer therapy. Copyright (C) 2011 S. Karger AG, Basel