PURPOSE: The antitumor effects of Interferon-beta (IFN-beta) are due to its direct inhibition of cell proliferation, immunostimulatory activity, and the inhibition of angiogenesis. We investigated the mechanism of the effects of IFN-beta on a murine colon 26 cell line (CT 26) and its highly metastatic variant (L5). METHODS: We examined its inhibitory effects on cell proliferation in vitro and the development of liver metastases in vivo. RESULTS: The proliferation of CT 26 in vitro was inhibited by IFN-beta in a dose- and time-dependent manner. The number of metastases was reduced in mice inoculated with CT 26 (P<0.01) and L5 (P<0.01) on Day 14 after treatment with IFN-beta. The median survival rate of the mice inoculated with L5 administered IFN-beta every other day, or every day was higher than in the control group (P<0.05). A dorsal air sac assay demonstrated that IFN-beta inhibited angiogenesis in mice inoculated with CT 26, but the effects disappeared with aminoguanidine, an inducible nitric oxide synthase inhibitor. CONCLUSION: These results showed that IFN-beta directly inhibits the proliferation of CT 26. In addition, the in vivo experiments suggested that IFN-beta might effectively inhibit liver metastases.
PURPOSE: The antitumor effects of Interferon-beta (IFN-beta) are due to its direct inhibition of cell proliferation, immunostimulatory activity, and the inhibition of angiogenesis. We investigated the mechanism of the effects of IFN-beta on a murine colon 26 cell line (CT 26) and its highly metastatic variant (L5). METHODS: We examined its inhibitory effects on cell proliferation in vitro and the development of liver metastases in vivo. RESULTS: The proliferation of CT 26 in vitro was inhibited by IFN-beta in a dose- and time-dependent manner. The number of metastases was reduced in mice inoculated with CT 26 (P<0.01) and L5 (P<0.01) on Day 14 after treatment with IFN-beta. The median survival rate of the mice inoculated with L5 administered IFN-beta every other day, or every day was higher than in the control group (P<0.05). A dorsal air sac assay demonstrated that IFN-beta inhibited angiogenesis in mice inoculated with CT 26, but the effects disappeared with aminoguanidine, an inducible nitric oxide synthase inhibitor. CONCLUSION: These results showed that IFN-beta directly inhibits the proliferation of CT 26. In addition, the in vivo experiments suggested that IFN-beta might effectively inhibit liver metastases.
Authors: R M Goldberg; S H Kaufmann; P Atherton; J A Sloan; A A Adjei; H C Pitot; S R Alberts; J Rubin; L L Miller; C Erlichman Journal: Ann Oncol Date: 2002-10 Impact factor: 32.976
Authors: L H Wong; K G Krauer; I Hatzinisiriou; M J Estcourt; P Hersey; N D Tam; S Edmondson; R J Devenish; S J Ralph Journal: J Biol Chem Date: 1997-11-07 Impact factor: 5.157