A recombinant cell-permeable p53 fusion protein is selectively stabilized under hypoxia and inhibits tumor cell growth
A recombinant cell-permeable p53 fusion protein is selectively stabilized under hypoxia and inhibits tumor cell growth
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重组细胞渗透性p53融合蛋白在缺氧下选择性稳定并抑制肿瘤细胞生长
DOI：
10.1016/j.canlet.2009.01.030
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发表时间：
2009-06-28
期刊：
影响因子：
9.7
通讯作者：
Wang, Yuxia
中科院分区：
文献类型：
--
作者：
Zhao, Yu;Wu, Junhua;Wang, Yuxia
超过50%的人类肿瘤含有p53突变。超过90%的肿瘤是实体瘤。实体瘤具有低含氧区域，称为缺氧区域，其中肿瘤细胞比其良好含氧的对应物对放射治疗和化学治疗更具抗性。在这项研究中，我们构建了一个细胞渗透性的p53融合蛋白，在缺氧区域具有选择性的稳定性。融合蛋白含有跨膜转导的达特肽、缺氧诱导因子-1 α的氧依赖性降解结构域和野生型p53。这种蛋白质被有效地递送到肿瘤细胞中，在那里它发挥抗癌活性，导致体外癌细胞生长的抑制和体内肿瘤重量的减少。因此，该融合蛋白可能成为一种新型的抗肿瘤治疗蛋白药物，特别是对缺氧肿瘤细胞的治疗。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
More than 50% of human tumors contain a mutation in p53. Over 90% of tumors are solid tumors. Solid tumors have low oxygenated regions, called hypoxic regions where the tumor cells are more resistant to radio- and chemo-therapy than their well-oxygenated counterparts. In this study, we constructed a cell-permeable p53 fusion protein with selective stability in the hypoxic region. The fusion protein contained the TAT peptide for transduction across membranes, the oxygen-dependent degradation domain of hypoxia-inducible factor-1alpha and wild-type p53. This protein was effectively delivered into tumor cells where it exerted anticancer activity leading to the inhibition of cancer cell growth in vitro and the reduction of tumor weight in vivo. Hence, the fusion protein can be a novel protein drug for antitumor therapies, especially for hypoxic tumor cells. (C) 2009 Elsevier Ireland Ltd. All rights reserved.