Pigment epithelium-derived factor inhibits glioma cell growth in vitro and in vivo.
Glioblastoma multiforme is the most common malignant brain tumor in adults, and it is among the most lethal of all cancers. Recent studies have shown that pigment epithelium-derived factor (PEDF) can induce differentiation and inhibit angiogenesis of several tumors. This study was designed to determine whether gliomas angiogenesis and tumor growth could be inhibited by PEDF. We found that PEDF down-regulated expression levels of vascular endothelial growth factor and up-regulated the expression of thrombospondin-2 and augmented apoptosis in a dose-dependent manner in both A172 and U87 glioma cells lines after 48 h of treatment. Analysis of the cell cycle showed arrest in the G(1) phase and block in S phase of the cell cycle. Meanwhile PEDF induced apoptosis was associated with increases of p53 and Bax and inhibition of Bcl-2. Conditioned medium with PEDF showed a significantly reductive effect on migration in vitro accompanied with a significant reduction of matrix metalloproteinase-9 expression. PEDF suppressed glioma cell migration in vitro and tumor burden in athymic nude mice. These results demonstrate for the first time inhibitory effects of PEDF on the growth and migration of human gliomas via induction of apoptosis and blocking of migratory-related factors. PEDF activation can be a novel approach for future therapeutic purposes against gliomas.
Zhang
Tao
T
Center of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, 12 Central Urumqi Road, Shanghai 200040, China.
Guan
Ming
M
Xu
Chong
C
Chen
Yuming
Y
Lu
Yuan
Y
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001932:Brain Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005136:Eye Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015552:Injections, Intralesional; D051379:Mice; D009368:Neoplasm Transplantation; D009414:Nerve Growth Factors / Q000494:pharmacology* / Q000627:therapeutic use; D015843:Serpins / Q000494:pharmacology* / Q000627:therapeutic use; D000099174:Pigment Epithelium-Derived Factor
D020533:Angiogenesis Inhibitors; D051017:Apoptosis Regulatory Proteins; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor