Effects of ibuprofen on the in vitro invasiveness of a human transitional cell carcinoma.
Non-steroidal anti-inflammatory drugs, such as ibuprofen, have demonstrated significant anti-cancer activity in both animals and humans. We examined the anti-invasive effects of ibuprofen on the human UM-UC urinary bladder carcinoma cell line using a rapid in vitro tumor cell invasion assay. The inhibitory effects of ibuprofen on the invasiveness and motility of the human UM-UC transitional cell carcinoma (TCC) cell line were evaluated using Matrigel coated polycarbonate filters (8 microns pore size) from Transwell cluster plates. In addition, the potential role of prostaglandin E2 in this process was examined. Ibuprofen exposure at non-cytotoxic concentrations resulted in a significant (p < 0.05) dose-dependent reduction of invasion when compared to vehicle exposed controls. Even at the highest concentration, ibuprofen had no effect on the rate of tumor cell division. Similarly, the highest concentration of ibuprofen did not alter tumor cell motility through uncoated 8 microns-pore polycarbonate filters. Addition of both prostaglandin E2 and ibuprofen to the culture medium restored tumor cell invasiveness through Matrigel-coated membranes to levels nearly identical to vehicle exposed controls (DMSO-no ibuprofen). The results indicate that ibuprofen is effective in preventing tumor cell invasion in this in vitro model. Prostaglandin E2 reverses the anti-invasive effects of ibuprofen. The anti-invasive effect of ibuprofen warrants further study alone or in combination with other therapies used in the treatment of early stage transitional cell carcinoma of the urinary bladder.
Cook
G P
GP
Department of Urology, Medical College of Ohio Toledo 43614, USA.
Hampton
J A
JA
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015232:Dinoprostone; D007052:Ibuprofen