Fang Fang, Chen Ping, Wu Xin, Yang Li, Yang Xun, Xi Zhen-Xiang, Zhou Bin-Wen, Zhou Xi-Kun, Qian Zhi-Yong, Xiao Bo, Wei Yu-Quan
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, 610041 Chengdu, People's Republic of China.
J Cancer Res Clin Oncol. 2009 Sep;135(9):1149-57. doi: 10.1007/s00432-009-0555-y. Epub 2009 Feb 15.
Malignant pleural effusion (MPE) is a common clinical problem in patients with advanced cancer. Evidence suggests that tumor-mediated angiogenesis and enhanced vascular permeability in the pleural wall are due to high levels of vascular endothelial growth factor (VEGF), which plays an important role in the pathogenesis of MPE. The present study was designed to test whether the recombinant adenovirus-mediated delivery of human endostatin (Ad-hEndo), one of the potent inhibitors of angiogenesis, would inhibit the formation and progression of MPE.
We developed a novel mouse model of MPE by injecting Lewis lung carcinoma (LLC) cells directly into pleural cavity of C57BL/6 mice. To evaluate the therapeutic effects of endostatin in this MPE model, we injected the Ad-hEndo into the pleural cavity of MPE-bearing mice three times with the 3-day interval.
We found that this treatment resulted in significant reduction in pleural effusion volume, the number of pleural tumor foci, microvessel density, and vascular permeability, while it significantly prolonged the survival time. In addition, VEGF level of MPE in the group administered with the Ad-hEndo was obviously decreased as compared with that in the two control groups administered with null-adenovirus (Ad-null) or normal saline.
Our work provides a rationale for future studies toward evaluating the effectiveness of the adenovirus-based endostatin therapy for MPE.
恶性胸腔积液（MPE）是晚期癌症患者常见的临床问题。有证据表明，肿瘤介导的血管生成以及胸膜壁血管通透性增加是由高水平的血管内皮生长因子（VEGF）引起的，VEGF在MPE的发病机制中起重要作用。本研究旨在测试重组腺病毒介导的人类内皮抑素（Ad-hEndo）（一种有效的血管生成抑制剂）的递送是否会抑制MPE的形成和进展。
我们通过将Lewis肺癌（LLC）细胞直接注射到C57BL/6小鼠的胸腔中，建立了一种新型的MPE小鼠模型。为了评估内皮抑素在该MPE模型中的治疗效果，我们以3天的间隔向携带MPE的小鼠胸腔内注射Ad-hEndo三次。
我们发现这种治疗导致胸腔积液量、胸膜肿瘤灶数量、微血管密度和血管通透性显著降低，同时显著延长了生存时间。此外，与注射空腺病毒（Ad-null）或生理盐水的两个对照组相比，注射Ad-hEndo组的MPE中VEGF水平明显降低。
我们的工作为未来评估基于腺病毒载体的内皮抑素治疗MPE的有效性的研究提供了理论依据。
