Adenovirus-mediated intra-tumoral delivery of the human endostatin gene inhibits tumor growth in nasopharyngeal carcinoma
Adenovirus-mediated intra-tumoral delivery of the human endostatin gene inhibits tumor growth in nasopharyngeal carcinoma
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DOI：
10.1002/ijc.21585
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发表时间：
2006-04-15
影响因子：
6.4
通讯作者：
Huang, WL
中科院分区：
文献类型：
--
作者：
Li, L;Liu, RY;Huang, WL
鼻咽癌是我国南方最常见的恶性肿瘤之一，其生长和转移与肿瘤血管生成密切相关。在这里，我们研究是否肿瘤内递送内皮抑素基因可以导致长期的局部表达的生物活性内皮抑素在治疗水平。我们构建了携带人内皮抑素基因的重组腺病毒载体（Ad/hEndo），在鼻咽癌CNE-2细胞中高效表达内皮抑素蛋白，并在体外显著抑制血管内皮细胞的增殖和迁移。Ad/hEndo体内治疗NPC CNE-2移植瘤5个疗程后，肿瘤生长和血管生成明显受到抑制。肿瘤组织中的Endostatin mRNA在给药后1-2天达到峰值，1周内消失，而血浆Endostatin蛋白水平在给药后3天达到峰值，持续2-3周。治疗相关的内皮抑制素转基因表达在多次肿瘤内施用Ad/hEndo的过程中实现。多次注射腺病毒载体不会导致血清中腺病毒中和抗体的持续增加。因此，腺病毒介导的人内皮抑素基因的肿瘤内导入可能形成一种可行的NPC新治疗方法，尽管每2-3周重新给药可能是最佳效果所必需的。(c)2005 Wiley-Liss，Inc.
The growth and metastasis of nasopharyngeal carcinoma (NPC), one of the most common cancers in southern China, is closely related to neovascularization. Here, we examined whether intratumoral delivery of endostatin gene could lead to long-term local expression of bioactive endostatin at therapeutic levels. We constructed a recombinant adenoviral vector carrying the human endostatin gene (Ad/hEndo), which expressed high-level endostatin protein in NPC CNE-2 cells, and significantly inhibited the proliferation and migration of vascular endothelial cells in vitro. Tumor growth and angiogenesis in NPC CNE-2 xenografted tumors were significantly inhibited after 5 courses of intra-tumoral treatment with Ad/hEndo in vivo. Endostatin mRNA in tumor tissues peaked at 1-2 days after intra-tumoral administration and disappeared within I week, whereas the plasma endostatin protein levels peaked at 3 days after administration and lasted 2-3 weeks. The therapeutically relevant endostatin transgene expression was achieved during the course of multiple intra-tumoral administrations with Ad/hEndo. Multiple injections with adenoviral vectors did not lead to continuous increases of adenovirus neutralizing antibodies in serum. Thus, adenovirus-mediated intra-tumoral introduction of the human endostatin gene may form a viable new treatment for NPC, although readministration every 2-3 weeks may be necessary for the best effect. (c) 2005 Wiley-Liss, Inc.