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The new synthetic matrix metalloproteinase inhibitor (Roche 28-2653) reduces tumor growth and prolongs survival in a prostate cancer standard rat model

Oncogene volume 21, pages 2089–2096 (2002)Cite this article

Abstract

The therapeutic efficacy of synthetic inhibitors of matrix-metalloproteinases (MMPs) in various cancers has been demonstrated. A novel inhibitor, Ro 28-2653, with high selectivity for MMP2, MMP9 and membrane type 1-MMP was evaluated in an orthotopic prostate cancer rat model. Efficacy was determined by recording tumor growth and survival endpoints. Prostate cancer was induced by inoculating R3327 Dunning tumor cells (MatLyLu) into the ventral lobe of the prostates of 148 Copenhagen rats. Daily oral treatment with Ro 28-2653 (10–300 mg/kg per day) was started on day 1 or on day 6 after tumor cell injection. Animals were sacrificed on day 20 for determination of tumor weights. For survival studies, rats received daily oral Ro 28-2653 (100 mg/kg per day) or vehicle for up to 30 days. Tumor induction was successful in 100% of the animals. Ro 28-2653 reproducibly reduced the tumor weights by up to 90% in a dose-dependent manner. In addition, an inhibitory effect in rats with established tumors (treatment start at day 6) was shown. A significantly prolonged survival of Ro 28-2653-treated rats was also demonstrated. Selective inhibition of MMP activity is a novel therapeutic approach, which bears promise for studies in patients with prostate cancer.

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Acknowledgements

The authors thank Sabine Becker, Silke Klotzek and Ines Baumert for valuable technical assistance. This work was supported by Roche Diagnostics GmbH, Germany. The study contains part of the doctoral thesis of W Rothaug.

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Authors and Affiliations

  1. Department of Urology, University Hospital Charité, Humboldt University Berlin, Berlin, 10098, Germany

    Michael Lein, Klaus Jung, Carsten Stephan, Winfried Rothaug, Manfred Johannsen, Serdar Deger, Dietmar Schnorr & Stefan Loening

  2. Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Bernhard Ortel

  3. Roche Diagnostics GmbH, Pharma Research Penzberg, Germany

    Rolf Juchem & Hans-Willi Krell

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  1. Michael Lein
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Correspondence to Michael Lein.

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Lein, M., Jung, K., Ortel, B. et al. The new synthetic matrix metalloproteinase inhibitor (Roche 28-2653) reduces tumor growth and prolongs survival in a prostate cancer standard rat model. Oncogene 21, 2089–2096 (2002). https://doi.org/10.1038/sj.onc.1205267

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