Targeting the IGF-1R using picropodophyllin in the therapeutical 5T2MM mouse model of multiple myeloma: beneficial effects on tumor growth, angiogenesis, bone disease and survival

Int J Cancer. 2007 Oct 15;121(8):1857-61. doi: 10.1002/ijc.22845.


During the last decade, a central role for insulin-like growth factor 1 (IGF-1) in the pathophysiology of multiple myeloma (MM) has been well established. IGF-I provided by the tumor-microenvironment interaction may directly and indirectly facilitate the migration, survival and expansion of the MM cells in the bone marrow (BM). The inhibition of the IGF-1R-mediated signaling pathway has recently been suggested to be a possible new therapeutic principle in MM. Using the mouse 5T2MM model, we now demonstrate that targeting the IGF-1R using picropodophyllin (PPP) in a therapeutical setting not only has strong antitumor activity on the established MM tumor but also influences the BM microenvironment by inhibiting angiogenesis and bone disease, having a profound effect on the survival of the mice. At therapeutically achievable concentrations of PPP, the average survival was 180 days for the PPP-treated mice as compared to 100 days for vehicle-treated mice. PPP used as single drug treatment in the 5T2MM model resulted in a decrease of tumor burden by 65% while the paraprotein concentrations were reduced by 75%. This decrease was associated with a significant inhibition of tumor-associated angiogenesis and osteolysis. The present studies on the biological effects of PPP in the 5T2MM model constitute an important experimental platform for future therapeutic implementation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Bone Neoplasms / prevention & control*
  • Disease Models, Animal
  • Kaplan-Meier Estimate
  • Mice
  • Multiple Myeloma / blood supply
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Neovascularization, Pathologic / prevention & control*
  • Podophyllotoxin / analogs & derivatives*
  • Podophyllotoxin / pharmacology
  • Receptor, IGF Type 1 / drug effects*


  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • picropodophyllin
  • Receptor, IGF Type 1
  • Podophyllotoxin