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Pigment epithelium-derived factor enhances tumor response to radiation through vasculature normalization in allografted lung cancer in mice

Cancer Gene Therapy volume 22, pages 181–187 (2015)Cite this article

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Abstract

This study aimed to explore the potential therapeutic effects of the combination of pigment epithelium-derived factor (PEDF) and radiation on lung cancer. The Lewis lung cancer (LLC) allografts in nude mice were treated with radiation, PEDF and PEDF combined with radiation. The morphologic changes of tumor vasculature and the hypoxic fraction of tumor tissues were evaluated. Significant inhibition of tumor growth was observed when radiation was applied between the 3rd and 7th day (the vasculature normalization window) after the initiation of PEDF treatment. During the vasculature normalization window, the tumor blood vessels in PEDF-treated mice were less tortuous and more uniform than those in the LLC allograft tumor treated with phosphate-buffered saline. Meanwhile, the thickness of the basement membrane was remarkably reduced and pericyte coverage was significantly increased with the PEDF treatment. We also found that tumor hypoxic fraction decreased during the 3rd to the 7th day after PEDF treatment, suggesting improved intratumoral oxygenation. Taken together, our results show that PEDF improved the effects of radiation therapy on LLC allografts by inducing a vascular normalization window from the 3rd to the 7th day after PEDF treatment. Our findings provide a basis for treating lung cancer with the combination of PEDF and radiation.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (30872974, 81172116 and 81201736), the Science and Technology Planning Project of Guangdong Province, China (2009B030801154) and the Plan of Financial Support for the R&D of Dongguan’s Higher Education, Scientific Research and Medical Institutions.

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Author notes

  1. Z Xu, Y Dong, F Peng and Z Yu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Province, Guangzhou, China,

    Z Xu, F Peng, X Hu, Q Zhou, Y Bao & M Chen

  2. Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong Province, China

    Z Xu, Z Yu & Y Zuo

  3. Cancer Center, 3rd People’s Hospital, Dongguan City, Guangdong Province, China

    Y Dong

  4. Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China

    Z Dai & G Gao

  5. Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China

    Y Chen, J Wang & H Ma

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  1. Z Xu
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Correspondence to M Chen.

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Xu, Z., Dong, Y., Peng, F. et al. Pigment epithelium-derived factor enhances tumor response to radiation through vasculature normalization in allografted lung cancer in mice. Cancer Gene Ther 22, 181–187 (2015). https://doi.org/10.1038/cgt.2014.79

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  • DOI: https://doi.org/10.1038/cgt.2014.79

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