title: Interleukin 12 and indomethacin exert a synergistic, angiogenesis-dependent antitumor activity in mice.
abstract: Nonsteroidal anti-inflammatory drugs have been shown to reduce the incidence and mortality from colorectal cancer. It has recently been demonstrated that these drugs are capable of suppressing the production of pro-angiogenic factors from tumor cells. The mechanisms of antitumor action of interleukin 12 include the enforced secretion of anti-angiogenic factors and stimulation of antitumor immunity. Therefore, we hypothesized that the combination of a model nonsteroidal anti-inflammatory drug--indomethacin and interleukin 12--would result in enhanced angiogenesis-dependent antitumor effects against a colon-26 carcinoma cells transplanted into syngeneic mice. As expected the combined administration of both agents simultaneously resulted in a strengthened antitumor activity that was manifested as a retardation of tumor growth and prolongation of mouse survival. Importantly some mice were completely cured after the combined treatment. As administration of interleukin 12 and indomethacin resulted in enhanced inhibition of angiogenesis it seems possible that prevention of new blood vessel formation is one of the mechanisms responsible for the observed antitumor effects.
authors.affiliation: Department of Immunology, Institute of Biostructure, The Medical University of Warsaw, Poland. jgolab@ib.amwaw.edu.pl
authors.forename: J
authors.initials: J
authors.lastname: Gołab
authors.forename: K
authors.initials: K
authors.lastname: Kozar
authors.forename: R
authors.initials: R
authors.lastname: Kamiński
authors.forename: A
authors.initials: A
authors.lastname: Czajka
authors.forename: M
authors.initials: M
authors.lastname: Marczak
authors.forename: T
authors.initials: T
authors.lastname: Switaj
authors.forename: A
authors.initials: A
authors.lastname: Giermasz
authors.forename: T
authors.initials: T
authors.lastname: Stokłosa
authors.forename: W
authors.initials: W
authors.lastname: Lasek
authors.forename: R
authors.initials: R
authors.lastname: Zagozdzon
authors.forename: K
authors.initials: K
authors.lastname: Mucha
authors.forename: M
authors.initials: M
authors.lastname: Jakóbisiak
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D007213:Indomethacin / Q000008:administration & dosage / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009389:Neovascularization, Pathologic; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D018664:Interleukin-12; D007213:Indomethacin