title: Inhibition of insulin like growth factor II autocrine growth of Wilms' tumor by suramin in vitro and in vivo.
abstract: Suramin was found to affect the Wilms' tumor (WT) cell line, W13, by inhibiting in vitro growth (half-maximal inhibitory dose (ID50)=11 microM), insulin like growth factor II (IGF-II) cell binding (ID50 = 10 microM) and IGF-II induced DNA synthesis (ID50 = 8 microM). In addition, suramin inhibited cross-linking of [125I]IGF-II to the type 1 IGF receptor (IGF1R) and type 2 IGF receptor (IGF2R). Disruption of IGF-II/IGF1R interaction appears to be the main mode of action of suramin since the suramin response was abolished in the presence of the IGF1R blocking antibody, alpha IR-3. When administered to athymic mice bearing W13 heterotransplants, suramin suppressed the linear tumor growth rate by 64%.
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: T S
authors.initials: TS
authors.lastname: Vincent
authors.forename: D J
authors.initials: DJ
authors.lastname: Hazen-Martin
authors.forename: A J
authors.initials: AJ
authors.lastname: Garvin
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D008940:Mitotic Index; D011869:Radioligand Assay; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D017527:Receptor, IGF Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology* / Q000627:therapeutic use; D013936:Thymidine / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D009396:Wilms Tumor / Q000188:drug therapy / Q000473:pathology*
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D017527:Receptor, IGF Type 2; D013498:Suramin; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D013936:Thymidine