Down-regulation of S-phase kinase associated protein 2 (Skp2) induces apoptosis in oral cancer cells
Down-regulation of S-phase kinase associated protein 2 (Skp2) induces apoptosis in oral cancer cells
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DOI：
10.1016/j.oraloncology.2005.02.007
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发表时间：
2005-07-01
期刊：
影响因子：
4.8
通讯作者：
Sato, M
中科院分区：
文献类型：
--
作者：
Harada, K;Supriatno;Sato, M
S相蛋白相关蛋白2(Skp2)是干细胞因子泛素-蛋白连接酶复合体底物识别亚单位F-box家族的成员，参与泛素介导的哺乳动物G期进展的几个关键调控因子的降解，包括细胞周期蛋白依赖的激酶抑制因子p27(Kip1)，一种剂量依赖的肿瘤抑制蛋白。在两种同样表现出Skp2蛋白过度表达的口腔癌细胞系中，证实了该反义效应。在这项研究中，我们在体内外研究了反义抑制口腔癌细胞生长的机制。Skp2反义治疗诱导细胞凋亡，表现为早期细胞凋亡增多，细胞核碎裂，caspase-3、-8、-9活化。此外，Skp2反义治疗显著抑制了移植瘤的生长。此外，组织学标本显示，Skp2反义治疗的肿瘤细胞凋亡增加。我们的结果表明，Skp2的下调似乎可以诱导口腔癌细胞的凋亡，靶向该分子可能是治疗这种类型癌症的一种有前途的新方法。(C)2005爱思唯尔有限公司。保留所有权利。
S-phase kinase associated protein 2 (Skp2) is a member of an F-box family of substrate-recognition subunits of SCF ubiquitin-protein ligase complexes that has been implicated in the ubiquitin-mediated degradation of several key regulators of mammalian G, progression, including the cyclin-dependent kinase inhibitor p27(Kip1), a dosage-dependent tumor suppressor protein. The anti-sense effect was confirmed in two cell lines of oral cancer cells that also exhibited over-expression of the Skp2 protein. In this study, we examined the mechanism responsible for anti-sense-mediated growth inhibition of oral cancer cells in vitro and in vivo. Skp2-anti-sense treatment induced apoptosis characterized by an increase in the early apoptosis, fragmentation of nuclei and activation of caspase-3, -8 and -9. Moreover, the growth of xenograft tumors was markedly suppressed by Skp2-antisense treatment. Furthermore, histological specimen revealed apoptotic cell death was increased in Skp2-anti-sense treated tumors. Our results suggest that down-regulation of Skp2 appears to induce apoptosis in oral cancer cells, targeting this molecule could represent a promising new therapeutic approach for this type of cancer. (c) 2005 Elsevier Ltd. All rights reserved.