Synergistic antiproliferative activity of human fibroblast interferon in combination with alpha-difluoromethylornithine against human gastric cancer cells in vitro.
The author has studied the effects of alpha-difluoromethylornithine (alpha DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase; human fibroblast interferon (IFN beta); and their combination on human gastric cancer cell growth in vitro. alpha DFMO (from 0.1 to 4 mmol/l) inhibited cell growth in a dose-dependent manner. Both alpha DFMO (0.1 mmol/l) and higher doses of IFN beta (100 and 1000 IU/ml) caused only limited inhibition of cell growth. When alpha DFMO (0.1 mmol/l) was administered in combination with IFN beta (100 and 1000 IU/ml), synergistic antiproliferative activity was observed 7 days after continuous exposure. Although the mechanisms by which this effect occurs are unclear, it appears to be associated with direct inhibition of tumor cell proliferation, possibly by modulation of polyamine metabolism.
Kubota
S
S
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D015317:Biogenic Polyamines / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000518:Eflornithine / Q000494:pharmacology*; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D015317:Biogenic Polyamines; D016899:Interferon-beta; D000518:Eflornithine