Interferon-alpha inhibits cyclooxygenase-1 and stimulates cyclooxygenase-2 expression 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 responses, carcinogenesis, and tumor angiogenesis. The formation of PGs is stimulated in various cancers since the expression of Cox-2 is upregulated. Interferon (IFN)-alpha is used in the treatment of bladder cancer, although not all of the effects of such treatment are thoroughly known. Therefore, we investigated the expression of cyclooxygenases in two bladder cancer cell lines, 5637 and T24, under basal conditions and in the presence of human recombinant 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, respectively. In contrast, Cox-2 expression increased in both cell lines. In 5,637 cells, Cox-2 expression increased 1.3-fold with 10,000 U/ml of IFN-alpha. In 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 upregulated 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.
Boström
P J
PJ
Department of Surgery, Turku University Central Hospital, Turku, Finland.
Uotila
P
P
Rajala
P
P
Nurmi
M
M
Huhtaniemi
I
I
Laato
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism; D002295:Carcinoma, Transitional Cell; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms
D000970:Antineoplastic Agents; D016898:Interferon-alpha; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases