Human endostatin inhibits growth of human non-small-cell lung cancer in a murine xenotransplant model

Overall prognosis in human NSCLC remains poor. Antiangiogenic treatment has become a promising concept for the treatment of solid malignancies. Our pu rpose was to evaluate the efficacy of recombinant HSENDO for the treatment of human NSCLC in an orthotopic murine xenotransplantation model. The effic acy of HSENDO was tested in vitro in cell-proliferation, cell-migration and tube-formation assays. In vivo, the effect of HSENDO on tumor growth was t ested in s.c. xenotransplanted human NSCLC and on intrapulmonary induced hu man NSCLC. In vitro, HSENDO inhibited both human and rodent endothelial cel l proliferation in a time- and dose-dependent fashion. Endothelial cell mig ration was inhibited by 97%. Tube formation of murine endothelial cells was inhibited and preexisting tubes degenerated after HSENDO exposure. In vivo , HSENDO delayed growth of s.c. xenotransplanted tumors. Immunohistochemic staining demonstrated no change in microvessel density but a significant re duction of proliferating tumor cells and an,inc ease bFGF and VEGF expressi on, reflecting the ant angiogenic effect of HSENDO. Intrapulmonary tumor in duction caused death subsequent to metastatic disease. Systemic HSENDO appl ication extended survival significantly. HSENDO was demonstrated to inhibit endothelial cell proliferation, migration and tube formation effectively. In vivo growth of s.c. transplanted tumors was delayed and survival extende d by 32% and 69%, respectively, after intrapulmonary NSCLC induction. (C) 2 001 Wiley-Liss, Inc.