Suppression of angiogenesis and therapy of human colon cancer liver metastasis by systemic administration of interferon-α1

S. Ozawa, H. Shinohara, H. O. Kanayama, C. J. Bruns, C. D. Bucana, L. M. Ellis, D. W. Davis, I. J. Fidler

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

The purpose of this study was to determine whether systemic administration of interferon-alpha (IFN-α) can inhibit liver metastasis produced in nude mice by human colon cancer cells. KM12L4 (IFN-α-sensitive) or KM12L4 IFNR (IFN-α- resistant) cells were injected into the spleen of nude mice. Seven days later, the mice were treated with subcutaneous (s.c.) injections of IFN-α (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 metalloproteinase-9 (MMP-9) mRNA and protein occurred in mice given daily injections of IFN-α. Kinetic analysis of therapy showed that daily s.c. administrations of 10,000 units of IFN-α induced apoptosis in liver metastasis - associated endothelial cells, followed by inhibition of tumor cell division and apoptosis of tumor cells. These data suggest that the antiangiogenic activity of IFN-α2a depends on frequent administration of the optimal biologic dose.

Original languageEnglish (US)
Pages (from-to)154-164
Number of pages11
JournalNeoplasia
Volume3
Issue number2
DOIs
StatePublished - 2001

Keywords

  • Angiogenesis
  • Apoptosis
  • Interferon

ASJC Scopus subject areas

  • Cancer Research

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