We examined the effects of IGF-I (1-1000 ng/ml) on cell proliferation in LM2d6 mouse fibroblast cells at 0.1, 1.0 and 5.0% fetal bovine serum (FBS). In medium containing 0.1% FBS, treatment of LM2d6 cells with IGF-I significantly reduced the cell number in a dose- and time-dependent manner, whereas no effects were seen at 1 or 5% FBS. Treatment of the cells with 0.1% FBS for 72 h caused DNA laddering and nuclear condensation. However, Scatchard analysis for IGF-I binding sites on the cells revealed that both the number and the affinity of IGF-I receptors were not greater than that of Balb/3T3 cells. Furthermore, the apoptotic action of Long (R(3))-IGF-I, an analogue of IGF-I that has a reduced affinity for IGF binding proteins, was not greater than that of IGF-I. Taken together, we conclude that IGF-I reduces cell proliferation at low levels of FBS due to the induction of apoptosis. This effect is probably not caused by an excess production of IGF binding proteins in LM2d6 cells.
Copyright 2001 Academic Press.