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 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%.
Vincent
T S
TS
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston 29425, USA.
Hazen-Martin
D J
DJ
Garvin
A J
AJ
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*
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