Suppression of angiogenesis and therapy of human colon cancer liver metastasis by systemic administration of interferon-alpha

The purpose of this study was to determine whether systemic administration of interferon-alpha (IFN-LU) can inhibit liver metastasis produced in nude mice by human colon cancer cells. KM12L4 (IFN-alpha -sensitive) or KM12L4 I FNR (IFN-alpha -resistant) cells were injected into the spleen of nude mice . Seven days later, the mice were treated with subcutaneous (s.c.) injectio ns of IFN-alpha (70,000 units/week) at different dosing schedules (1, 2, or 7 times/week). Significant inhibition of tumor growth, vascularization and expression of basic fibroblast growth factor (bFGF) or matrix metalloprote inase-9 (MMP-9) mRNA and protein occurred in mice given daily injections of IFN-alpha. Kinetic analysis of therapy showed that daily s.c. administrati ons of 10,000 units of IFN-alpha induced apoptosis in liver metastasis-asso ciated endothelial cells, followed by inhibition of tumor cell division and apoptosis of tumor cells. These data suggest that the antiangiogenic activ ity of IFN-alpha -2a depends on frequent administration of the optimal biol ogic dose.