Insulin-like growth factor binding protein-6 and CCI-779, an ester analogue of rapamycin, additively inhibit rhabdomyosarcoma growth

Horm Metab Res. 2003 Nov-Dec;35(11-12):822-7. doi: 10.1055/s-2004-814153.


Rhabdomyosarcomas secrete high levels of insulin-like growth factor-II, suggesting this autocrine growth factor plays a major role in the unregulated growth of this childhood cancer. Treatment of Rh30 rhabdomyosarcoma cells with insulin-like growth factor binding protein-6 (IGFBP-6; 1000 ng/ml), which binds insulin-like growth factor-II with high affinity, inhibited growth in vitro (p < 0.001). Co-incubation of cells with rapamycin (1.56 ng/ml), an inhibitor of p70 S6 kinase, and IGFBP-6 (200 ng/ml) resulted in a significant reduction in Rh30 cell number compared to rapamycin or IGFBP-6 alone (p < 0.05 for both). Co-treatment of Rh30 cells with CCI-779 (5 and 50 ng/ml), an ester analogue of rapamycin, and IGFBP-6 (200 or 1000 ng/ml) also inhibited growth in vitro relative to CCI-779 alone (p < 0.01 and p < 0.001, respectively). In a nude mouse model, xenografts of Rh30 cells transfected with a recombinant vector encoding IGFBP-6 (phBP6-E3) showed delayed growth relative to vector control xenografts (27 days vs. 19 days to reach an average tumour volume of 0.5 cm (3); p < 0.001). Treatment with CCI-779 (10 mg/kg) of mice inoculated with vector control xenografts, also delayed growth (to 31 days; p = 0.0055) relative to untreated mice with vector control xenografts. Co-treatment with CCI-779 (10 mg/kg) reduced phBP6-E3 transfected xenograft growth even further (to 45 days) compared to vector control xenografts (p < 0.001, day 33). CCI-779 thus acts additively with IGFBP-6 to reduce rhabdomyosarcoma growth both in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects*
  • Cell Line
  • Cell Line, Tumor
  • Humans
  • Insulin-Like Growth Factor Binding Protein 6 / pharmacology*
  • Kidney
  • Kinetics
  • Mice
  • Mice, Nude
  • Recombinant Proteins / pharmacology
  • Rhabdomyosarcoma / pathology*
  • Sirolimus / analogs & derivatives*
  • Sirolimus / pharmacology*
  • Transplantation, Heterologous


  • Insulin-Like Growth Factor Binding Protein 6
  • Recombinant Proteins
  • temsirolimus
  • Sirolimus