Combined targeting of the VEGFr/EGFr and the mammalian target of rapamycin (mTOR) signaling pathway delays cell cycle progression and alters adhesion behavior of prostate carcinoma cells

Steffen Wedel; Lukasz Hudak; Jens-Michael Seibel; Eva Juengel; Igor Tsaur; Axel Haferkamp; Roman A Blaheta

doi:10.1016/j.canlet.2010.11.003

Combined targeting of the VEGFr/EGFr and the mammalian target of rapamycin (mTOR) signaling pathway delays cell cycle progression and alters adhesion behavior of prostate carcinoma cells

Cancer Lett. 2011 Feb 1;301(1):17-28. doi: 10.1016/j.canlet.2010.11.003. Epub 2010 Nov 30.

Authors

Steffen Wedel¹, Lukasz Hudak, Jens-Michael Seibel, Eva Juengel, Igor Tsaur, Axel Haferkamp, Roman A Blaheta

Affiliation

¹ Department of Urology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.

PMID: 21122981
DOI: 10.1016/j.canlet.2010.11.003

Abstract

The impact of the mTOR inhibitor RAD001 combined with the EGFr/VEGFr tyrosine kinase inhibitor AEE788 on prostate tumor cell growth, adhesion and migration was analyzed in vitro. The RAD001-AEE788 combination profoundly reduced tumor-endothelium and tumor-matrix contacts, suppressing cell growth and cell cycle progression. The underlying molecular mode of action depended on the cell phenotype, since cell cycle proteins, integrin subtype expression and integrin dependent signaling were altered in a different manner in PC-3 and DU-145 versus LNCaP prostate cancer cells. Simultaneous targeting of mTOR and VEGFr/EGFr related pathways may offer a novel therapeutic strategy for prostate cancer treatment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Adhesion / drug effects
Cell Cycle / drug effects
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
ErbB Receptors / antagonists & inhibitors*
ErbB Receptors / physiology
Everolimus
Humans
Male
Neoplasm Invasiveness
Prostatic Neoplasms / drug therapy*
Prostatic Neoplasms / pathology
Protein Kinase Inhibitors / pharmacology*
Protein Kinase Inhibitors / therapeutic use
Purines / pharmacology
Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
Receptors, Vascular Endothelial Growth Factor / physiology
Signal Transduction / drug effects*
Sirolimus / analogs & derivatives
Sirolimus / pharmacology
TOR Serine-Threonine Kinases / antagonists & inhibitors*
TOR Serine-Threonine Kinases / physiology

Substances

Protein Kinase Inhibitors
Purines
Everolimus
MTOR protein, human
ErbB Receptors
Receptors, Vascular Endothelial Growth Factor
TOR Serine-Threonine Kinases
AEE 788
Sirolimus