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Electrochemotherapy is effective in the treatment of rat bone metastases

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Abstract

Bone metastases impair general health status, quality of life and survival of patients. Electrochemotherapy (ECT), which combines electroporation (EP) and the administration of anticancer drugs, has been recently introduced into clinical practice for the local treatment of solid tumours. In the present study, the ability of EP with bleomycin (Bleo) to induce MRMT-1 rat breast cancer cell death was investigated in vitro. Then, an in vivo model for bone metastases was set up by the inoculation of MRMT-1 cells in rat proximal tibia. 7 days after tumour induction the animals were treated with Bleo, EP, Bleo followed by EP (ECT), or left untreated. ECT eliminated the tumour in 6 out of 8 (75 %) treated metastases. Radiological evaluation showed that the Honore score in ECT-treated animals was significantly lower when compared with the other groups (p < 0.0005) and not significantly different from healthy controls. Bone morphology in ECT-treated animals, evaluated by histological and microtomographical analyses, showed intact cortical and trabecular bone structure with new bone apposition. Histomorphometric evaluation showed that ECT-treated metastases had significantly higher bone volume, trabecular number, trabecular thickness and bone mineral density compared with those of untreated metastases (respectively p < 0.0005 for BV/TV, Tb.N and BMD; p < 0.05 for Tb.Th) or metastases treated with Bleo (p < 0.05 for BV/TV, Tb.N, p < 0.005 for BMD) or EP (p < 0.005 for BV/TV, Tb.N; p < 0.0005 for BMD). These findings suggest that early ECT treatment of bone metastases is minimally invasive, safe and effective, thus providing pre-clinical evidence for its use in the treatment of human bone metastases.

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Acknowledgments

This paper is dedicated to the memory of Prof. Mario Mercuri († 7/05/2011), an inspiring guide and example who has contributed to this study with his enthusiasm, incitement and support. Moreover, this study would not have been the same without the valuable and constructive assistance of Dr. Marco Alberghini († 27/06/2012), who helped the authors with his knowledge and friendship during histology and data analysis. The authors are grateful to Fondazione Carisbo for their financial support. The research was also financed by Istituto Ortopedico Rizzoli and funds 5 × 1,000 (year 2008–2009).

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  1. Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy

    Milena Fini, Lucia Martini & Melania Maglio

  2. Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, BITTA, Rizzoli Orthopaedic Institute, Bologna, Italy

    Milena Fini, Francesca Salamanna, Annapaola Parrilli, Lucia Martini & Veronica Borsari

  3. I Orthopaedics and Trauma Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy

    Matteo Cadossi

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  1. Milena Fini
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Fini, M., Salamanna, F., Parrilli, A. et al. Electrochemotherapy is effective in the treatment of rat bone metastases. Clin Exp Metastasis 30, 1033–1045 (2013). https://doi.org/10.1007/s10585-013-9601-x

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