Role of nitric oxide in human gastric cancer cells treated with 5-fluorouracil

We examined whether 5-fluorouracil (5-FU) induces nitric oxide (NO) product ion and evaluated the role of NO in antitumor activity in human gastric can cer cells. MKN-1 gastric cancer cells were treated with the IC50 of 5-FU in the presence of interferon-gamma (IFN-gamma). In addition, s-methyl isothi ourea tan antagonist of inducible nitric oxide synthase) or anti-TNF-alpha antibody was added to the culture medium. Production of NO was measured by nitrite assay, TNF-alpha was measured by enzyme-linked immunoabsorbent assa y, antitumor activity was evaluated by 3-[4,5-dimethylethiazol-2-yl]-2,5-di pheniltetrasolium bromide (MTT) assay. After 5-FU treatment in the presence of IFN-gamma, NO and TNF-alpha were produced and anti-tumor activity was e nhanced. In contrast, s-methylisothiourea abolished the antitumor activity of 5-FU treatment. Anti-TNF-alpha antibody inhibited NO production and decr eased the antitumor activity. 5-FU induces NO production by gastric cancer cells, and NO participates in anti-tumor activity in gastric cancer cells. These effects may be mediated by TNF-alpha production.