Therapeutic effects of recombinant human endostatin adenovirus in a mouse model of malignant pleural effusion

Fang Fang, Ping Chen, Xin Wu, Li Yang, Xun Yang, Zhen Xiang Xi, Bin Wen Zhou, Xi Kun Zhou, Zhi Yong Qian, Bo Xiao, Yu Quan Wei

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1149-1157
Number of pages9
JournalJournal of Cancer Research and Clinical Oncology
Volume135
Issue number9
DOIs
StatePublished - Sep 1 2009

Keywords

  • Intrapleural administration
  • Malignant pleural eVusion
  • Recombinant human endostatin adenovirus
  • Therapeutic eVects
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Fang, F., Chen, P., Wu, X., Yang, L., Yang, X., Xi, Z. X., Zhou, B. W., Zhou, X. K., Qian, Z. Y., Xiao, B., & Wei, Y. Q. (2009). Therapeutic effects of recombinant human endostatin adenovirus in a mouse model of malignant pleural effusion. Journal of Cancer Research and Clinical Oncology, 135(9), 1149-1157. https://doi.org/10.1007/s00432-009-0555-y