Stimulation of Tumor Growth by Recombinant Human Insulin-like Growth Factor-I (IGF-I) Is Dependent on the Dose and the Level of IGF-I Receptor Expression

摘要: The insulin-like growth factors (IGF) I and II regulate metabolism, mitogenesis, differentiation, apoptosis. therapeutic uses of IGF-I have been discussed extensively; however, excessive activity the IGF ligands receptor has suggested as a factor in tumorigenesis. inhibition apoptosis by is believed to be particularly important for stimulation tumor growth. This study examined whether systemic recombinant human (rhIGF-I) therapy affects fibrosarcomas derived from fibroblasts expressing at high or naturally occurring densities (1.9 × 105 compared with 1.6 104 receptors/cell) athymic nude mice. Treatment 4 10 mg/kg rhIGF-I resulted marked reduction latency stimulated that overexpressed receptor. parental levels were not affected therapy. Analysis mitosis histone H3 mRNA situ hybridization terminal deoxynucleotidyl transferase-mediated nick end labeling assay indicated rhIGF-I-stimulated was associated increase mitogenesis; there no evidence any significant effect on These data imply that: ( ) can stimulate tumors directly stimulating mitosis; b reasonable level expression required rhIGF-I.