Human endostatin inhibits growth of human non-small-cell lung cancer in a murine xenotransplant model
Human endostatin inhibits growth of human non-small-cell lung cancer in a murine xenotransplant model
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DOI：
10.1002/ijc.1471
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发表时间：
2001-11-01
影响因子：
6.4
通讯作者：
Neumaier, M
中科院分区：
文献类型：
--
作者：
Boehle, AS;Kurdow, R;Neumaier, M
人类非小细胞肺癌的总体预后仍然较差。抗血管生成治疗已成为治疗实体恶性肿瘤的一个有前途的概念。我们的目的是在原位鼠异种移植模型中评估重组 HSENDO 治疗人类 NSCLC 的疗效。 HSENDO 的功效在体外细胞增殖、细胞迁移和管形成试验中进行了测试。在体内，皮下测试了 HSENDO 对肿瘤生长的影响。异种移植的人类 NSCLC 和肺内诱导的人类 NSCLC。在体外，HSENDO 以时间和剂量依赖性方式抑制人类和啮齿动物内皮细胞增殖。内皮细胞迁移被抑制97%。暴露于 HSENDO 后，小鼠内皮细胞的管形成受到抑制，并且先前存在的管退化。在体内，HSENDO 延迟了皮下细胞的生长。异种移植肿瘤。免疫组织化学染色显示微血管密度没有变化，但增殖的肿瘤细胞显着减少，bFGF 和 VEGF 表达增加，反映了 HSENDO 的抗血管生成作用。肺内肿瘤诱导导致转移性疾病后死亡。全身应用 HSENDO 显着延长了生存期。 HSENDO 被证明可以有效抑制内皮细胞增殖、迁移和管形成。皮下细胞的体内生长肺内 NSCLC 诱导后，移植肿瘤延迟，生存期分别延长 32% 和 69%。 (C) 2001 Wiley-Liss, Inc.
Overall prognosis in human NSCLC remains poor. Antiangiogenic treatment has become a promising concept for the treatment of solid malignancies. Our purpose was to evaluate the efficacy of recombinant HSENDO for the treatment of human NSCLC in an orthotopic murine xenotransplantation model. The efficacy of HSENDO was tested in vitro in cell-proliferation, cell-migration and tube-formation assays. In vivo, the effect of HSENDO on tumor growth was tested in s.c. xenotransplanted human NSCLC and on intrapulmonary induced human NSCLC. In vitro, HSENDO inhibited both human and rodent endothelial cell proliferation in a time- and dose-dependent fashion. Endothelial cell migration was inhibited by 97%. Tube formation of murine endothelial cells was inhibited and preexisting tubes degenerated after HSENDO exposure. In vivo, HSENDO delayed growth of s.c. xenotransplanted tumors. Immunohistochemic staining demonstrated no change in microvessel density but a significant reduction of proliferating tumor cells and an,inc ease bFGF and VEGF expression, reflecting the ant angiogenic effect of HSENDO. Intrapulmonary tumor induction caused death subsequent to metastatic disease. Systemic HSENDO application extended survival significantly. HSENDO was demonstrated to inhibit endothelial cell proliferation, migration and tube formation effectively. In vivo growth of s.c. transplanted tumors was delayed and survival extended by 32% and 69%, respectively, after intrapulmonary NSCLC induction. (C) 2001 Wiley-Liss, Inc.