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Molecular Medicine

, Volume 14, Issue 7–8, pp 403–411 | Cite as

Rosiglitazone Attenuates Insulin-Like Growth Factor 1 Receptor Survival Signaling in PC-3 Cells

  • Efstathia Papageorgiou
  • Nea Pitulis
  • Menelaos Manoussakis
  • Peter Lembessis
  • Michael Koutsilieris
Research Article

Abstract

PPARγ, a member of the peroxisome proliferator-activated receptor family, is overexpressed in prostate cancer. Natural and synthetic ligands of PPARγ via genomic and nongenomic actions promote cell cycle arrest and apoptosis of several prostate cancer cells, in vitro. Insulin-like growth factor 1 (IGF-1) inhibits the adriamycin-induced apoptosis of PC-3 human prostate cancer cells. Therefore, we have analyzed the ability of two PPARγ ligands,15dPGJ2 and rosiglitazone, a natural and a synthetic PPARγ ligand, respectively, to increase the adriamycin-induced cytotoxicity of PC-3 cells and to suppress the IGF-1 survival effect on adriamycin-induced apoptosis of PC-3 cells. Our data revealed that both the PPARγ ligands increased the adriamycin-induced cytostasis of PC-3 cells, however, only rosiglitazone added to the adriamycin-induced apoptosis of PC-3 cells. In addition, rosiglitazone attenuated the type I IGF receptor (IGF-1R) survival signaling on adriamycin-induced apoptosis of PC-3 cells via its nongenomic action on ERK1/2 and AKT phosphorylation. Because the IGF-1R signaling is probably the most important host tissue (bone) metastasis microenvironment-related survival signaling for prostate cancer cells, we conclude that rosiglitazone effects on IGF-1R-mediated activation of ERK1/2 and AKT could have clinical implications for the management of androgen ablation-refractory and chemotherapy-resistant advanced prostate cancer with bone metastasis.

Notes

Acknowledgment

The authors would like to thank Prof. Athanasios Papavassiliou for comments and suggestions regarding the context of this manuscript.

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Copyright information

© Feinstein Institute for Medical Research 2008

Authors and Affiliations

  • Efstathia Papageorgiou
    • 1
  • Nea Pitulis
    • 1
  • Menelaos Manoussakis
    • 2
  • Peter Lembessis
    • 1
  • Michael Koutsilieris
    • 1
  1. 1.Department of Experimental Physiology, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  2. 2.Department of Pathophysiology, Medical SchoolNational and Kapodistrian University of Athens, GoudiAthensGreece

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