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  • Original Article
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Sonoporation-mediated anti-angiogenic gene transfer into muscle effectively regresses distant orthotopic tumors

Cancer Gene Therapy volume 19, pages 171–180 (2012)Cite this article

Abstract

Ultrasound (US) is an effective tool for local delivery of genes into target tumors or organs. In combination with microbubbles, US can temporarily change the permeability of cell membranes by cavitation and facilitate entry of plasmid DNA into cells. Here, we demonstrate that repeated US-mediated delivery of anti-angiogenic genes, endostatin or calreticulin, into muscle significantly inhibits the growth of orthotopic tumors in the liver, brain or lung. US-mediated anti-angiogenic gene therapy also seems to function as an adjuvant therapy that significantly enhances the antitumor effects of the chemotherapeutic drug doxorubicin and adenovirus-mediated cytokine gene therapy. Significantly higher levels of tumor apoptosis or tumor-infiltrating lymphocytes were observed after combined therapy consisting of either anti-angiogenic therapy and chemotherapy, or anti-angiogenic therapy and immunotherapy. Taken together, our experiments demonstrate that intramuscular delivery of anti-angiogenic genes by US exposure can effectively treat distant orthotopic tumors, and thus has great therapeutic potential in terms of clinical treatment.

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Acknowledgements

This work was supported by Grant NSC 99-2320-B-002-005-MY3 to W-SC from the National Science Council of the Republic of China, and in part by a grant from the Ministry of Education, Aim for the Top University Plan to L-HH.

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Author notes

  1. Z-K Liao and K-C Tsai: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan

    Z-K Liao & L-H Hwang

  2. Graduate Institute of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan

    Z-K Liao, H-T Wang & L-H Hwang

  3. Institute of Biomedical Engineering, National Taiwan University College of Medicine, Taipei, Taiwan

    K-C Tsai

  4. Department of Surgery, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

    S-H Tseng

  5. Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan

    W-P Deng

  6. Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

    W-S Chen

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Correspondence to W-S Chen or L-H Hwang.

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Liao, ZK., Tsai, KC., Wang, HT. et al. Sonoporation-mediated anti-angiogenic gene transfer into muscle effectively regresses distant orthotopic tumors. Cancer Gene Ther 19, 171–180 (2012). https://doi.org/10.1038/cgt.2011.73

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