Interferon-alpha inhibits cyclooxygenase-1 and stimulates cyclooxygenase-2expression in bladder cancer cells in vitro

The enzymes cyclooxygenase-1 (Cox-1) and cyclooxygenase-2 (Cox-2) catalyze the initial step in the formation of prostaglandins (PGs). PGs are known to be involved in numerous processes, for example inflammation, immune respon ses, carcinogenesis, and tumor angiogenesis. The formation of PGs is stimul ated in various cancers since the expression of Cox-2 is upregulated. Inter feron (IFN)-alpha is used in the treatment of bladder cancer, although not all of the effects of such treatment are thoroughly known. Therefore, we in vestigated the expression of cyclooxygenases in two bladder cancer cell lin es, 5637 and T24, under basal conditions and in the presence of human recom binant IFN-alpha (100, 1,000, and 10,000 U/ml). The mRNA of Cox-1 and Cox-2 was expressed in both cultured bladder carcinoma cell lines. The level of Cox-1 expression was low in 5637 cells and higher in T24 cells. In contrast , Cox-2 expression was prominent in 5637 cells and low in T24 cancer cells. The highest IFN-alpha concentration (10,000 U/ml) decreased the expression of Cox-1 to 47 and 28% of the control levels in 5637 and T24 cells, respec tively. In contrast, Cox-2 expression increased in both cell lines. In 5,63 7 cells, Cox-2 expression increased 1.3-fold with 10,000 U/ml of IFN-alpha. III T24 cells, the maximum effect was achieved by 1,000 U/ml of IFN-alpha, which increased the expression of Cox-2 up to 2.4-fold. These findings may have relevance in the outcome of patients treated with IFN-alpha because u pregulated Cox-2 expression may suppress the cell-mediated defense system. On the other hand, the inhibition of Cox-1 could be beneficial because Cox- 1 is known to stimulate angiogenesis.