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Peroxisome proliferator-activated receptor γ ligands inhibit VEGF-mediated vasculogenic mimicry of prostate cancer through the AKT signaling pathway.
- Source :
-
Molecular medicine reports [Mol Med Rep] 2014 Jul; Vol. 10 (1), pp. 276-82. Date of Electronic Publication: 2014 Apr 29. - Publication Year :
- 2014
-
Abstract
- Vasculogenic mimicry (VM) describes functional vascular channels composed only of tumor cells and its presence predicts a poor prognosis for patients with prostate cancer. The present study demonstrated that prostate cancer PC-3 cells were able to form a patterned matrix or tubular VM in 3D cultures in vitro and rosiglitazone (RSG), the ligand of peroxisome proliferator-activated receptor γ (PPARγ) and effectively inhibited the formation of VM structures in a dose- and PPARγ‑dependent manner. In addition, RSG significantly inhibited prostate cancer cell migration and invasion. The inhibitory effect of RSG on VM formation could be at least partially explained by an RSG-driven downregulation of vascular endothelial growth factor (VEGF) levels and phosphorylation of AKT, which is known to be important in VM. Furthermore, the present study highlighted that VEGF and the phosphoinositide 3-kinase/AKT pathway exert a positive feedback regulation in the process of VM formation. These findings reveal new therapeutic potential for PPARγ ligands in anti‑cancer therapy.
- Subjects :
- Cell Culture Techniques
Cell Line, Tumor
Cell Movement drug effects
Down-Regulation drug effects
Humans
Ligands
Male
Neovascularization, Pathologic
PPAR gamma metabolism
Phosphatidylinositol 3-Kinases metabolism
Phosphorylation drug effects
Prostatic Neoplasms metabolism
Prostatic Neoplasms pathology
Recombinant Proteins biosynthesis
Recombinant Proteins genetics
Recombinant Proteins pharmacology
Rosiglitazone
Vascular Endothelial Growth Factor A genetics
Vascular Endothelial Growth Factor A metabolism
PPAR gamma agonists
Proto-Oncogene Proteins c-akt metabolism
Signal Transduction drug effects
Thiazolidinediones pharmacology
Vascular Endothelial Growth Factor A pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1791-3004
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular medicine reports
- Publication Type :
- Academic Journal
- Accession number :
- 24787994
- Full Text :
- https://doi.org/10.3892/mmr.2014.2198