Effect of Endostatin on Preventing Postoperative Progression of Distant Metastasis in a Murine Lung Cancer Model
Effect of Endostatin on Preventing Postoperative Progression of Distant Metastasis in a Murine Lung Cancer Model
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DOI：
10.1177/030089161109700617
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发表时间：
2011-11
期刊：
影响因子：
1.9
通讯作者：
Helan Wang;T. Ning;Mei Li;Zejun Lu;Xi Yan;Q. Peng;Na Lei;Hui Zhang;F. Luo
中科院分区：
文献类型：
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作者：
Helan Wang;T. Ning;Mei Li;Zejun Lu;Xi Yan;Q. Peng;Na Lei;Hui Zhang;F. Luo
目的和背景癌症的复发和转移仍然是手术切除原发肿瘤后死亡的主要原因。术后全身血管生成活性的上调与远处肿瘤转移之间存在正相关。在本研究中，我们建立了一个自发转移模型，并研究是否使用内皮抑素抗血管生成治疗可以防止原发肿瘤切除后远处转移的进展。方法雌性C57 BL/6小鼠皮下接种1 × 106个刘易斯肺癌细胞。在植入癌细胞后20天，切除原发肿瘤，并将小鼠随机分为三组。NS组给予生理盐水，L-ES组给予内皮抑素3 mg/kg，H-ES组给予内皮抑素20 mg/kg，连续10 d。观察内皮抑素对肺转移瘤的抑制作用及小鼠生存时间。流式细胞术和免疫组化检测血管生成活性。采用酶联免疫吸附法检测外周血内皮抑素水平。结果NS组、L-ES组和H-ES组的肺转移结节平均数分别为10.2个、2.8个和4.0个;肺平均净重分别为0.55 g、0.31 g和0.36 g。NS组与内皮抑素治疗组比较差异有统计学意义（P <0.05）。内皮抑制素治疗组小鼠生存期延长（P <0.05）。与NS组相比，内皮抑素治疗组外周血循环内皮细胞水平降低，转移瘤微血管密度降低，L-ES组降低更明显（P <0.05）。随着对小鼠持续施用内皮抑制素，内皮抑制素的全身存在逐渐增加。结论内皮抑素抗血管生成治疗可有效抑制术后远处转移的进展。
Aims and Background The relapse and metastasis of cancer remain a predominant cause of death after surgical removal of the primary tumor. There is a positive linkage between the postoperative upregulation of systemic angiogenic activity and distant tumor metastasis. In the present study, we established a spontaneous metastasis model and investigated whether antiangiogenic therapy using endostatin could prevent the progression of distant metastasis after removal of the primary tumor. Methods Female C57BL/6 mice were implanted subcutaneously with 1 × 106 Lewis lung cancer cells. Twenty days after implantation of the cancer cells, the primary tumor was removed and the mice were randomly divided into three groups. The NS group received normal saline, the L-ES group received 3 mg/kg endostatin, and the H-ES group received 20 mg/kg endostatin intravenously daily for 10 days. The effect of endostatin on lung metastases and the survival time of the mice were observed. Flow cytometry and immunohistochemistry were carried out to assess the angiogenic activity. The serum endostatin levels in peripheral blood were measured using an enzyme-linked immunosorbent assay. Results The mean number of metastatic pulmonary nodules and the mean net lung weight in the NS, L-ES and H-ES groups was 10.2, 2.8 and 4.0, and 0.55g, 0.31g and 0.36g, respectively. The difference between the NS group and the endostatin-treated groups was statistically significant (P <0.05). The endostatin-treated mice showed prolonged overall survival (P <0.05). Compared with the NS group, the endostatin-treated groups had lower levels of circulating endothelial cells in peripheral blood and showed a decrease in microvessel density in the metastatic tumors, with a more marked reduction in the L-ES group (P <0.05). The systemic presence of endostatin was gradually increased with the continued administration of endostatin to the mice. Conclusions Antiangiogenic therapy with endostatin is effective in inhibiting the postoperative progression of distant metastasis.