INHIBITION OF INSULIN-LIKE GROWTH-FACTOR-II AUTOCRINE GROWTH OF WILMS-TUMOR BY SURAMIN IN-VITRO AND IN-VIVO

Suramin was found to affect the Wilms' tumor (WT) cell line, W13, by i nhibiting in vitro growth (half-maximal inhibitory dose (ID50) = 11 mu M), insulin like growth factor II (IGF-II) cell binding (ID50 = 10 mu M) and IGF-II induced DNA synthesis (ID50 = 8 mu M). In addition, sur amin inhibited cross-linking of [I-125]IGF-II to the type 1 IGF recept or (IGF1R) and type 2 IGF receptor (IGF2R). Disruption of IGF-II/IGF1R interaction appears to be the main mode of action of suramin since th e suramin response was abolished in the presence of the IGF1R blocking antibody, alpha IR-3. When administered to athymic mice bearing W13 h eterotransplants, suramin suppressed the linear tumor growth rate by 6 4%.