Annexin V-TRAIL fusion protein is a more sensitive and potent apoptotic inducer for cancer therapy.

Annexin V-TRAIL fusion protein is a more sensitive and potent apoptotic inducer for cancer therapy.
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膜联蛋白 V-TRAIL 融合蛋白是一种更敏感、更有效的癌症治疗细胞凋亡诱导剂

DOI:
10.1038/srep03565
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发表时间:
2013-12-20
期刊:
影响因子:
4.6
通讯作者:
Hua ZC
Hua ZC
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Qiu F;Hu M;Tang B;Liu X;Zhuang H;Yang J;Hua ZC

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肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-related apoptosis-inducing ligand,TRAIL)是一种很有前途的肿瘤治疗剂,它选择性地杀死癌细胞,而不伤害正常细胞。然而,肿瘤细胞和患者对TRAIL诱导的凋亡的抗性限制了其进一步应用。本研究开发了一种嵌合蛋白Annexin V-TRAIL(命名为TP 8),其体外和体内功效均高于TRAIL,在体外,TP 8对一系列肿瘤细胞的EC 50远低于野生型TRAIL。在体内,TP 8能有效抑制肿瘤生长,延长A549、Colo 205和Bel 7402等多种肿瘤细胞的肿瘤倍增时间和肿瘤生长延迟时间。这项研究为治疗TRAIL耐药癌症提供了一种新的合理策略。
The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent, which kills cancer cells selectively, while leaving normal cells unharmed. However, the emerging resistance of tumor cells and patients to TRAIL-induced apoptosis limits its further application. In this study, we developed a chimeric protein Annexin V-TRAIL (designated as TP8) with higher efficacy than TRAIL bothin vitroandin vivo.In vitro, the EC50of TP8 on a series of tumor cells was much lower than wild-type TRAIL. Annexin V provided this recombinant protein with higher efficacy, while leaving tumor specificity of TRAIL unchanged since TP8 had no effects on normal cells.Invivo, TP8 effectively suppressed tumor growth and prolonged tumor doubling time and tumor growth delay time in mouse xenografts involving multiple cancer cell types including A549, Colo205 and Bel7402. This study provides a new rational strategy to treat TRAIL-resistant cancers.
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