Peroxisome proliferator-activated receptor γ ligands inhibit VEGF-mediated vasculogenic mimicry of prostate cancer through the AKT signaling pathway.
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.
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Liang
L
Qin
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Ye
Y
Ren
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
An-Min
AM
Chen
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Feng-Jing
FJ
Guo
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Fei
F
Xu
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Chen
C
Gong
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Peng
P
Cheng
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Yu
Y
Du
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Hui
H
Liao
D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008297:Male; D009389:Neovascularization, Pathologic; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects*; D045162:Thiazolidinediones / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D008024:Ligands; D047495:PPAR gamma; D011994:Recombinant Proteins; D045162:Thiazolidinediones; D042461:Vascular Endothelial Growth Factor A; D000077154:Rosiglitazone; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt