Interleukin 12 and indomethacin exert a synergistic, angiogenesis-dependent antitumor activity in mice

Nonsteroidal anti-inflammatory drugs have been shown to reduce the incidenc e and mortality from colorectal cancer. It has recently been demonstrated t hat these drugs are capable of suppressing the production of pro-angiogenic factors from tumor cells. The mechanisms of antitumor action of interleuki n 12 include the enforced secretion of anti-angiogenic factors and stimulat ion of antitumor immunity. Therefore, we hypothesized that the combination of a model nonsteroidal antiinflammatory drug - indomethacin and interleuki n 12 would result in enhanced angiogenesis-dependent antitumor effects agai nst a colon-26 carcinoma cells transplanted into syngeneic mice. As expecte d the combined administration of both agents simultaneously resulted in a s trengthened antitumor activity that was manifested as a retardation of tumo r growth and prolongation of mouse survival. Importantly some mice were com pletely cured after the combined treatment. As administration of interleuki n 12 and indomethacin resulted in enhanced inhibition of angiogenesis it se ems possible that prevention of new blood vessel formation is one of the me chanisms responsible for the observed antitumor effects.