Cyclin-mediated G1 arrest by celecoxib differs in low-versus high-grade bladder cancer.
BACKGROUND
Celecoxib and other non-steroidal anti-inflammatory drugs (NSAIDs) are being evaluated in the prevention of bladder and other cancers. Here we investigate molecular effects of celecoxib independent of cyclooxygenase (COX)-2 expression levels in urothelial carcinoma of the bladder.


METHODS
Low-grade RT-4 and high-grade UM-UC-3 bladder cancer cells were treated with 0-50 muM celecoxib. Growth, cell cycle and apoptosis were measured by crystal violet elution and flow cytometry. Western analysis was performed for COX-2, Rb, cyclin B1/D1, and phospho-cyclin B1/D1. COX-2 induction was achieved with phorbol ester.


RESULTS
Celecoxib inhibited growth of RT-4 and UM-UC-3, with G(1) cell cycle arrest and altered cyclin B1/D1 expression in RT-4, whereas Rb up-regulation occurred in UM-UC-3. Apoptosis occurred in both cell lines.


CONCLUSIONS
Celecoxib induces G(1) cell cycle arrest in low- and high-grade bladder cancer by different pathways. This heterogeneous molecular response supports combination approaches to prevention and treatment.
Gee
Jason R
JR
Department of Urology, William S. Middleton Memorial Veterans Hospital, and Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. Gee@urology.wisc.edu
Burmeister
Corrie B
CB
Havighurst
Thomas C
TC
Kim
Kyungmann
K
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D056744:Cyclin B1 / Q000096:biosynthesis*; D019938:Cyclin D1 / Q000096:biosynthesis*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D011720:Pyrazoles / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D013449:Sulfonamides / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; C530104:CCND1 protein, human; D056744:Cyclin B1; D011720:Pyrazoles; D016160:Retinoblastoma Protein; D013449:Sulfonamides; D019938:Cyclin D1; D051546:Cyclooxygenase 2; D000068579:Celecoxib