The anti-tumor role and mechanism of integrated and truncated PDCD5 proteins in osteosarcoma cells
The anti-tumor role and mechanism of integrated and truncated PDCD5 proteins in osteosarcoma cells
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DOI：
10.1016/j.cellsig.2012.04.011
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发表时间：
2012-08-01
影响因子：
4.8
通讯作者：
Bai, Xi-Zhuang
中科院分区：
文献类型：
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作者：
Han, Xiao-Rui;Sun, Yu;Bai, Xi-Zhuang
骨肉瘤是一种高度恶性的骨肿瘤。在这些研究中，细胞凋亡相关基因程序性细胞死亡5基因（PDCD5）及其各种片段在OS细胞系MG-63中过表达。在体内和体外鉴定PDCD5对MG-63细胞的作用。结果表明，PDCD5可诱导MG-63细胞凋亡和G(2)期阻滞。此外，在已建立的异种移植肿瘤中，PDCD5的表达与肿瘤大小和重量的减小有关。因此，这些小鼠的存活率明显高于不表达PDCD5的荷瘤小鼠。为了分析所涉及的信号通路，我们进行了western blotting。在这些实验中，PDCD5被发现抑制Ras/Raf/MEK/ERK信号通路，导致细胞周期蛋白B和CDK1的抑制。此外，ERK的下调导致caspase 3和caspase 9的激活。这些结果与过表达PDCD5观察到的G(2)相阻滞一致。然而，没有观察到G(1)相阻滞。因此，与细胞周期G(1)期相关的蛋白与PDCD5过表达一起过表达。总的来说，这些研究证明了PDCD5在OS细胞系MG-63中的抗肿瘤活性，并提供了相关机制的见解，可能导致新的OS治疗方法。(C) 2012爱思唯尔公司版权所有。
Osteosarcoma (OS) is a high-grade malignant bone tumor. In these studies, the cell apoptosis-related gene, programmed cell death 5 gene (PDCD5), and various fragments of it, were overexpressed in the OS cell line, MG-63. The effects of PDCD5 on MG-63 cells both in vivo and in vitro were then identified. Our results indicate that PDCD5 can induce apoptosis and G(2) phase arrest in MG-63 cells. Moreover, expression of PDCD5 in established xenografted tumors was associated with a decrease in tumor size and weight. Accordingly, the survival rate of these mice was significantly higher than that of mice bearing tumors that did not express PDCD5. To analyze the signaling pathway involved, western blotting was performed. In these assays, PDCD5 was found to inhibit the Ras/Raf/MEK/ERK signaling pathway, leading to inhibition of cyclin B and CDK1. In addition, down-regulation of ERK resulted in activation of caspase 3 and caspase 9. These results are consistent with the G(2) phase arrest observed with overexpression of PDCD5. However, a G(1) phase arrest was not observed. Therefore, proteins associated with the G(1) phase of the cell cycle were overexpressed in combination with PDCD5 overexpression. Overall, these studies demonstrate the anti-tumor activity of PDCD5 in the OS cell line, MG-63, and provide insight into relevant mechanisms that may lead to novel treatments for OS. (C) 2012 Elsevier Inc. All rights reserved.