Phosphatidylinositol 3-kinase inhibitor LY294002 suppresses proliferation and sensitizes doxorubicin chemotherapy in bladder cancer cells.

Abstract

BACKGROUND:

Phosphatidylinositol 3-kinase (PI3K)-AKT signaling is a well-characterized pathway involved in the 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, thus selectively inhibiting the PI3K-AKT nexus. The purpose of the present study was to examine whether PI3K inhibited by LY294002 had an effect on human bladder cancer cells.

METHODS:

After treatment with LY294002, MTT assay, 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 suppression in a dose-response manner. Also, PI3K/AKT signaling inhibitor LY294002 suppressed cell proliferation and enhanced the chemosensitivity of doxorubicin in human bladder cancer EJ cells. Furthermore, LY294002 increased cell apoptosis to doxorubicin.

CONCLUSION:

The augmentation of doxorubicin with 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.

• Authors: Deyao Wu, Jun Tao, Bin Xu, Weijie Qing, Pengchao Li, Qiang Lu, Wei Zhang
• Journal: Urologia internationalis (Urol Int) Vol. 87 Issue 1 Pg. 105-13 ( 2011) ISSN: 1423-0399 [Electronic] Switzerland
• PMID: 21597260 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 S. Karger AG, Basel.

Chemical References

• Antibiotics, Antineoplastic
• Chromones
• Morpholines
• Phosphoinositide-3 Kinase Inhibitors
• Protein Kinase Inhibitors
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Doxorubicin
• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt

Topics

• Antibiotics, Antineoplastic (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chromones (pharmacology)
• Dose-Response Relationship, Drug
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Humans
• Morpholines (pharmacology)
• Phosphatidylinositol 3-Kinase (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Phosphorylation
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Time Factors
• Urinary Bladder Neoplasms (enzymology, pathology)