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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

Our work provides a rationale for future studies toward evaluating the effectiveness of the adenovirus-based endostatin therapy for MPE.

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Acknowledgments

This work was financially supported by Chinese Key Basic Research Program (2004CB518807), the projects of National Natural Science Foundation of China, and National 973 Program. Since the area of Ad vector research is rapidly expending, it was impossible to cite all related references in this article. Our apologies are to all investigators whose work could not be cited.

Conflict of interest statement

There is no duality of interest that could be perceived to bias our work, acknowledging all financial support and any other personal connections.

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Authors and Affiliations

  1. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, 610041, Chengdu, People’s Republic of China

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

  2. Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, People’s Republic of China

    Fang Fang

  3. Department of Cardiothoracic Surgery, West China Hospital, Sichuan University, 610041, Chengdu, People’s Republic of China

    Xun Yang

  4. Department of Organismic and Evolutionary Biology, Harvard University Herbaria, 22 Divinity Avenue, Cambridge, MA, 02138, USA

    Zhen-Xiang Xi

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  1. Fang Fang
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  2. Ping Chen
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  3. Xin Wu
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  4. Li Yang
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  5. Xun Yang
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  11. Yu-Quan Wei
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Corresponding author

Correspondence to Yu-Quan Wei.

Additional information

F. Fang, P. Chen and X. Wu have equally contributed to this work.

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Fang, F., Chen, P., Wu, X. et al. Therapeutic effects of recombinant human endostatin adenovirus in a mouse model of malignant pleural effusion. J Cancer Res Clin Oncol 135, 1149–1157 (2009). https://doi.org/10.1007/s00432-009-0555-y

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  • DOI: https://doi.org/10.1007/s00432-009-0555-y

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