Low-dose endostatin normalizes the structure and function of tumor vasculature and improves the delivery and anti-tumor efficacy of cytotoxic drugs in a lung cancer xenograft murine model
Low-dose endostatin normalizes the structure and function of tumor vasculature and improves the delivery and anti-tumor efficacy of cytotoxic drugs in a lung cancer xenograft murine model
复制标题
低剂量内皮抑素使肿瘤脉管系统的结构和功能正常化，并提高肺癌异种移植小鼠模型中细胞毒药物的递送和抗肿瘤功效
DOI：
10.1111/j.1759-7714.2012.00111.x
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发表时间：
2012-08-01
期刊：
影响因子：
2.9
通讯作者：
Luo, Feng
中科院分区：
文献类型：
--
作者：
Ning, Tao;Jiang, Ming;Luo, Feng
简介：内皮抑素在一定程度上使肿瘤血管正常化。然而，肿瘤血管正常化的最佳时间窗和最佳药物剂量需要探索。本文研究了低剂量内皮抑素对肿瘤血管结构和功能的影响，以及细胞毒药物的释放和抗肿瘤疗效。方法：采用小剂量内皮抑素治疗小鼠肺癌移植瘤模型10天。使用各种技术评价肿瘤血管的结构和功能。在不同的时间表中添加了Paclitaxel。结果：内皮抑素引起微血管密度显著降低。内皮抑素治疗后肿瘤血管壁结构更好。内皮抑制素给药后第6天肿瘤血流灌注增加。在第3、6和10天，伊文思蓝外渗到肿瘤实质中减少。在第三天和第六天，内皮抑制素治疗的小鼠具有更大的紫杉醇递送。血管正常化的时间窗约为3至6天。在第1 - 3天和第4 - 6天，与紫杉醇的联合治疗显著抑制了肿瘤生长。结论：低剂量内皮抑素有助于肿瘤血管的正常化。这导致细胞毒性药物向肿瘤的递送得到改善，这与在正常化窗口期间与紫杉醇组合时的协同功效密切相关。
Introduction: To some extent endostatin normalizes tumor vasculature. However, the optimum time window and optimum drug dose for tumor vascular normalization need to be explored. Here we investigate the effect of low-dose endostatin on the structure and function of tumor vasculature and the delivery and anti-tumor efficacy of cytotoxic drugs. Methods: A lung cancer xenograft murine model was treated with low-dose endostatin for 10 days. The structure and function of the tumor vasculature were evaluated using various techniques. Paclitaxel was added in different schedules. Results: Endostatin caused a significant reduction in microvessel density. Tumor vascular walls after endostatin treatment were better structured. Tumor blood perfusion was increased on day six after endostatin administration. On days three, six, and 10, Evans blue extravasation into the parenchyma of tumors was decreased. On days three and six, endostatin-treated mice had greater paclitaxel delivery. The time window of vascular normalization was approximately three to six days. On days one to three, and days four to six, combined therapy with paclitaxel significantly inhibited tumor growth. Conclusions: Low-dose endostatin aids normalization of tumor vasculature. This resulted in improved delivery of cytotoxic drugs to the tumor, which closely correlates with synergistic efficacy when combined with paclitaxel during the normalization window.