May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Oral Picropodophyllin (PPP) Is Well Tolerated in vivo and Inhibits IGF-1R Expression and Growth of Uveal Melanoma
Author Affiliations & Notes
  • M.-A. Economou
    Dept of Ophthalmology, St Eriks Eye Hospital / Karolinska Institute, Stockholm, Sweden
    Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
  • S. Andersson
    Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
  • D. Vasilcanu
    Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
  • C. All-Ericsson
    Dept of Ophthalmology, St Eriks Eye Hospital / Karolinska Institute, Stockholm, Sweden
  • A. Girnita
    Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
  • L. Girnita
    Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
  • M. Axelson
    Department of Clinical Chemistry, Karolinska Institutet, Stockholm, Sweden
  • S. Seregard
    Dept of Ophthalmology, St Eriks Eye Hospital / Karolinska Institute, Stockholm, Sweden
  • O. Larsson
    Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
  • Footnotes
    Commercial Relationships  M. Economou, None; S. Andersson, None; D. Vasilcanu, None; C. All-Ericsson, None; A. Girnita, None; L. Girnita, None; M. Axelson, NOTHING TO DISCLOSE, P; S. Seregard, None; O. Larsson, NOTHING TO DISCLOSE, P.
  • Footnotes
    Support  King Gustaf V Jubilee Foundation, St Erik's Eye Hospital Research Foundation
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1506. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      M.-A. Economou, S. Andersson, D. Vasilcanu, C. All-Ericsson, A. Girnita, L. Girnita, M. Axelson, S. Seregard, O. Larsson; Oral Picropodophyllin (PPP) Is Well Tolerated in vivo and Inhibits IGF-1R Expression and Growth of Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1506. doi: https://doi.org/.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: : The cyclolignan picropodophyllin (PPP) efficiently blocks the activity of insulin-like growth factor-1 receptor (IGF-1R) and inhibits growth of uveal melanoma cells in vitro and in vivo. In this study, we aimed to investigate the efficiency of orally administered PPP on growth of uveal melanoma xenografts. Further, we focused on the effect of PPP on vascular endothelial growth factor (VEGF) in vivo and evaluated its effects in combination with other established anti-tumor agents in vitro.

Methods: : Four different uveal melanoma cell lines (OCM-1, OCM-3, OCM-8, 92-1) were treated with PPP alone and in combination with imatinib mesylate, cisplatin, 5-FU and doxorubicin. Cell viability was determined by XTT assay. SCID mice xenografted with uveal melanoma cells were used to determine anti-tumor efficacy of oral PPP in vivo. Tumor samples obtained from the in vivo experiments were analyzed for VEGF and IGF-1R expression by western blotting.

Results: : PPP was found to be superior to the other anti-tumor agents in killing uveal melanoma cells. Oral PPP inhibited uveal melanoma growth in vivo and was well tolerated by the animals. PPP decreased VEGF expression in the tumors.

Conclusions: : Oral PPP is well tolerated in vivo and caused total growth inhibition of uveal melanoma xenografts as well as it decreased the levels of VEGF in the tumors.

Keywords: pathology: experimental • uvea • oncology 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×