EFFECTS OF IBUPROFEN ON THE IN-VITRO INVASIVENESS OF A HUMAN TRANSITIONAL-CELL CARCINOMA

Non-steroidal anti-inflammatory drugs, such as ibuprofen, have demonst rated significant anti-cancer activity in both animals and humans. We examined the anti-invasive effects of ibuprofen on the human UM-UC uri nary bladder carcinoma cell line using a rapid in vitro tumor cell inv asion assay. The inhibitory effects of ibuprofen on the invasiveness a nd motility of the human UM-UC transitional cell carcinoma (TCC) cell line were evaluated using Matrigel(R) coated polycarbonate filters (8 mu m pore size) from Transwell(R) cluster plates. In addition, the pot ential role of prostaglandin E(2) in this process was examined. Ibupro fen exposure at non-cytotoxic concentrations resulted in a significant (p < 0.05) dose-dependent reduction of invasion when compared to vehi cle 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 u ncoated 8 mu m-pore polycarbonate filters. Addition of both prostaglan din E(2) and ibuprofen to the culture medium restored tumor cell invas iveness through Matrigel(R) - coated membranes to levels nearly identi cal to vehicle exposed controls (DMSO-no ibuprofen). The results indic ate that ibuprofen is effective in preventing tumor cell invasion in t his in vitro model. Prostaglandin E(2) reverses the anti-invasive effe cts of ibuprofen. The anti-invasive effect of ibuprofen warrants furth er study alone or in combination with other therapies used in the trea tment of early stage transitional cell carcinoma of the urinary bladde r.