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Tumor radiosensitization by gene therapy against endoglin

Cancer Gene Therapy volume 23, pages 214–220 (2016)Cite this article

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Abstract

Gene electrotransfer of plasmid encoding shRNA against endoglin exerts antitumor efficacy, predominantly by vascular targeted effect. As vascular targeting therapies can promote radiosensitization, the aim of this study was to explore this gene therapy approach with single and split dose of irradiation in an endoglin non-expressing TS/A mammary adenocarcinoma tumor model to specifically study the vascular effects. Intratumoral gene electrotransfer of plasmids encoding shRNA against endoglin, under the control of a constitutive or tissue-specific promoter for endothelial cells, combined with a single or three split doses of irradiations was evaluated for the antitumor efficacy and histologically. Both plasmids proved to be equally effective in tumor radiosensitization with 40–47% of tumor cures. The combined treatment induced a significant decrease in the number of blood vessels and proliferating cells, and an increase in levels of necrosis, apoptosis and hypoxia; therefore, the antitumor efficacy was ascribed to the interaction of vascular targeted effect of gene therapy with irradiation. Endoglin silencing by the shRNA technology, combined with electrotransfer and the use of a tissue-specific promoter for endothelial cells, proved to be a feasible and effective therapeutic approach that can be used in combined treatment with tumor irradiation.

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Acknowledgements

We acknowledge M Lavric for her help with cell cultures and tumor transplantation, A Prevc and K Znidar for help with histology, T Dolinsek for help with endoglin silencing experiments and V Todorovic for useful tips. The research was supported by Slovenian Research Agency (P3-0003, J3-4211, J3-6793) and conducted in the scope of LEA EBAM (French-Slovenian European Associated Laboratory: Pulsed Electric Fields Applications in Biology and Medicine) and is a result of networking efforts within the COST TD1104 Action.

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Authors and Affiliations

  1. Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia

    M Stimac, U Kamensek, M Cemazar, S Kranjc & G Sersa

  2. Faculty of Health Sciences, University of Primorska, Izola, Slovenia

    M Cemazar & A Coer

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  1. M Stimac
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  2. U Kamensek
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  3. M Cemazar
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  4. S Kranjc
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  5. A Coer
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  6. G Sersa
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Correspondence to G Sersa.

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Supplementary Information accompanies the paper on Cancer Gene Therapy website

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Stimac, M., Kamensek, U., Cemazar, M. et al. Tumor radiosensitization by gene therapy against endoglin. Cancer Gene Ther 23, 214–220 (2016). https://doi.org/10.1038/cgt.2016.20

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