Peroxisome proliferator-activated receptor γ ligands inhibit VEGF-mediated vasculogenic mimicry of prostate cancer through the AKT signaling pathway
Peroxisome proliferator-activated receptor γ ligands inhibit VEGF-mediated vasculogenic mimicry of prostate cancer through the AKT signaling pathway
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DOI：
10.3892/mmr.2014.2198
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发表时间：
2014-07-01
影响因子：
3.4
通讯作者：
Liao, Hui
中科院分区：
文献类型：
--
作者：
Qin, Liang;Ren, Ye;Liao, Hui
血管生成拟态是指仅由肿瘤细胞组成的功能性血管通道，它的存在预示着前列腺癌患者预后不良。本研究表明，前列腺癌PC-3细胞在体外3D培养中能够形成图案化的基质或管状VM，并与PPARγ的配体罗格列酮(RSG)呈剂量和PPARγ依赖的方式有效地抑制VM结构的形成。此外，RSG还能显著抑制前列腺癌细胞的迁移和侵袭。RSG对VM形成的抑制作用至少部分可以通过下调血管内皮细胞生长因子(VEGF)水平和AKT的磷酸化来解释，AKT在VM中起重要作用。此外，本研究还强调了血管内皮生长因子和肌醇磷脂3-激酶/AKT通路在VM形成过程中发挥正反馈调节作用。这些发现揭示了PPAR伽马配体在抗癌治疗中的新的治疗潜力。
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 gamma (PPAR gamma) and effectively inhibited the formation of VM structures in a dose-and PPAR gamma-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 PPAR gamma ligands in anti-cancer therapy.