Pigment epithelium-derived factor (PEDF)-induced apoptosis and inhibition of vascular endothelial growth factor (VEGF) expression in MG63 human osteosarcoma cells
Pigment epithelium-derived factor (PEDF)-induced apoptosis and inhibition of vascular endothelial growth factor (VEGF) expression in MG63 human osteosarcoma cells
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DOI：
10.1016/j.lfs.2005.05.048
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发表时间：
2005-11-04
期刊：
影响因子：
6.1
通讯作者：
Imaizumi, T
中科院分区：
文献类型：
--
作者：
Takenaka, K;Yamagishi, S;Imaizumi, T
色素上皮衍生因子（PEDF）已被证明是哺乳动物眼睛中最有效的血管生成抑制剂，因此表明PEDF的缺失与血管生成性眼病如增殖性糖尿病视网膜病变有关。肿瘤的生长和进展也需要血管生成。我们沿着其他人最近发现，PEDF可以通过其对肿瘤内皮细胞的抗血管生成作用来抑制裸鼠黑色素瘤和肝细胞癌的生长。然而，PEDF对肿瘤细胞的直接作用的可能性仍然存在。在这项研究中，我们研究了PEDF对MG 63人骨肉瘤细胞生长和血管内皮生长因子（VEGF）表达的影响。PEDF以剂量依赖性方式降低MG 63细胞的活细胞数以及DNA合成。此外，发现PEDF增加半胱天冬酶-3/7活性，并随后诱导MG 63细胞中的凋亡性细胞死亡。PEDF还在mRNA和蛋白水平上抑制MG 63细胞中VEGF的表达。我们目前的研究提供了PEDF对骨肉瘤细胞的新的有益方面;一个是诱导肿瘤细胞的凋亡性细胞死亡，另一个是抑制VEGF表达，这将导致抑制肿瘤血管生成。因此，PEDF可能是一种有前途的治疗骨肉瘤的药物。(c)2005年爱思唯尔公司All rights reserved.
Pigment epithelium-derived factor (PEDF) has been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, thus suggesting that loss of PEDF is involved in angiogenic eye diseases such as proliferative diabetic retinopathy. Angiogenesis is required for tumor growth and progression as well. We, along with others, have recently found that PEDF could inhibit growth of melanoma and hepatocellular carcinoma in nude mice through its anti-angiogenic effects on tumor endothelial cells. However, the possibility of the direct effect of PEDF on tumor cells has remained. In this study, we investigated the effects of PEDF on growth and vascular endothelial growth factor (VEGF) expression in MG63 human cultured osteosarcoma cells. PEDF decreased viable cell number as well as DNA synthesis in MG63 cells in a dose-dependent manner. Furthermore, PEDF was found to increase caspase-3/7 activity and to subsequently induce apoptotic cell death in MG63 cells. PEDF also inhibited VEGF expression in MG63 cells at both mRNA and protein levels. Our present study provides novel beneficial aspects of PEDF on osteosarcoma cells; one is induction of apoptotic cell death of tumor cells, and the other is the suppression of VEGF expression, which would lead to inhibition of tumor angiogenesis. PEDF therefore might be a promising therapeutic agent for treatment of patients with osteosarcoma. (c) 2005 Elsevier Inc. All rights reserved.